AUGUST 24, 2016
Molecular Foundations
Vesicular Trafficking
Course Directors:
Kelly Quesnelle, PhD
Melissa Olken, MD
WEDNESDAY, AUGUST 24, 2016
Resource for Independent Learning
Vesicular Trafficking
Bonny Dickinson, PhD
[email protected]
Expected time to complete: 50-100 minutes
In this iBook you will learn the basic
mechanisms of vesicular trafficking, which
includes: fluid phase and receptor-mediated
endocytosis, exocytosis, phagocytosis,
pinocytosis, recycling and transcytosis.
Copyright
Copyright © 2016
Western Michigan University
Homer Stryker M.D. School of
Medicine
All rights reserved. This iBook and the contents are the sole property of
Western Michigan University Homer
Stryker M.D. School of Medicine (WMed),
and are authorized for use only by WMed
students and faculty. No part of this
publication may be published, reproduced,
stored in a retrieval system, or transmitted
in any form or by any means including
mechanical, electronic, photocopying,
recording, or otherwise without the prior
written permission of WMed. Chapter 1
Learning Objectives
1. Define the following terms: cargo,
endocytosis, endocytic vesicle, phagocytosis,
phagosome, phagolysosome, pinocytosis,
lysosome, recycling, transcytosis, exocytosis,
clathrin, clathrin-coated pit, caveolin,
caveolae, autophagy, xenophagy, COP I &
COP II.
2. Explain the clinical relevance of vesicular
trafficking.
3. Compare and contrast pinocytosis (fluidphase endocytosis), receptor-mediated
endocytosis and phagocytosis.
4. Describe the three possible fates of cargo
internalized via receptor-mediated
endocytosis.
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5. Compare and contrast the fate of cargo
internalized via clathrin-coated pits and
caveolae.
6. Explain the purpose of exocytosis.
7. Explain how cargo is recycled.
8. Explain how cargo is transcytosed.
9. Explain the role of Rabs and SNAREs in
vesicular trafficking.
10. Describe the mechanisms by which
lysosomes acquire and degrade cargo.
Chapter 1, Section 1
Clinical Relevance
One of the most interesting areas of research in the field of cell biology is vesicular trafficking.
In 2013, three cell biologists were awarded the
Nobel Prize in Physiology or Medicine for their
contributions to understanding how the cell
organizes its transport systems. These Nobel
Laureates (Randy Schekman, Thomas Südhof
and James Rothman) discovered the major
molecular principles that govern how proteins
are delivered via vesicles to the right place in the cell.
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Their discoveries have also revealed how
defects in transport and delivery of cellular
proteins cause deleterious cellular effects and
contribute to neurological diseases, diabetes
and immunologic disorders.
To learn more about these discoveries, see:
http://www.hhmi.org/news/schekman-sudhofawarded-2013-nobel-prize-physiology-ormedicine
Chapter 2
In Preparation
There are no pre-reading assignments
in preparation for this event.
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Chapter 3
Vesicular Trafficking
Have you ever wondered how
immunoglobulins (antibodies) such as IgG, IgM and IgA are transported from the blood to mucosal surfaces such as the gut, lung and
genitourinary tract where they provide an
essential defense against bacteria, viruses and
parasites? This is an amazing process termed
transcytosis (transport across the cell) and
requires specialized receptors that pick up
immunoglobulins on one side of the epithelial
cells lining these mucosal surfaces, enclose it in
a membrane vesicle and transport it across the
interior of the cell to the opposite membrane
where it is released when the vesicle fuses with
the membrane.
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In this iBook you will learn about the different
vesicular transport mechanisms by which
proteins such as hormones, immunoglobulins
and neurotransmitters, are moved around
within cells and into and out of cells so that they
can do what they need to do where they need to
do it.
Chapter 3, Section 1
Chapter 3 Table of Contents
Section 1: Table of Contents
Section 9: Receptor-mediated Endocytosis
Section 2: Basic Terminology
Section 10: Recycling
Section 3: Introduction to Vesicular Trafficking
Section 11: Transcytosis
Section 4: Endocytosis
Section 12: Exocytosis
Section 5: Phagocytosis
Section 13: SNAREs & Rabs
Section 6: Pinocytosis
Section 14: Lysosomes
Section 7: Clathrin Coated Pits & Clathrin
Coated Vesicles
Section 15: Autophagy & Xenophagy
Section 8: Caveolae
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Section 16: Summary
Chapter 3, Section 2
Basic Terminology
Transport of molecules within and into and out of the cell occurs through various processes.
To understand these various pathways, let’s first learn some basic terminology.
1. Cargo refers to anything that can be taken
into and transported within a cell through
the process of vesicular trafficking. Some
examples of cargoes are: hormones,
immunoglobulins, neurotransmitters,
bacteria, viruses and apoptotic cells.
2. Endocytosis refers to the uptake of cargo
into a cell by invagination of the plasma
membrane and its internalization in an
endosome, a membrane-bound vesicle
containing cargo for sorting. There are three
main forms of endocytosis: pinocytosis,
receptor-mediated endocytosis and
phagocytosis.
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3. Pinocytosis is a form of endocytosis in
which soluble materials (fluids and solutes)
are taken up from the extracellular
environment and incorporated into vesicles
for digestion. Literally, pinocytosis is “cell
drinking.” Pinocytosis is also termed fluidphase endocytosis.
4. Receptor-mediated endocytosis, as the
name suggests, this requires that a specific
receptor bind to and transport a cargo into
the cell. Such transport receptors can be
found associated with specialized plasma
membrane domains rich in clathrin or
caveolae (discussed in the following below).
Chapter 3, Section 2
Basic Terminology
5. Phagocytosis (from Greek phagein,
meaning to eat) is the process by which
particulate (non-soluble) material, such
microorganisms or dead cells, is
endocytosed. This largely occurs in immune
cells termed phagocytes (macrophages and
neutrophils). Note that the term “phagocyte”
refers to a cell that performs phagocytosis.
Phagocytosis involves the uptake of
particulate cargo into large vesicles called
phagosomes.
6. Lysosome. In general, when cargo is taken
into the cell and enclosed in an endosome, it
has one of three fates. It can be degraded in a
specialized organelle termed a lysosome, it
can be recycled back out of the cell in a
process appropriately termed recycling, or
it can be taken from one pole of the cell to
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the opposite pole via transcytosis.
Transcytosis occurs in “polarized” cells such
as intestinal epithelial cells that have
functionally and morphologically distinct
membrane domains termed apical (faces a
lumen) and basolateral (composed of lateral
membranes that make cell-to-cell
connections and the basal membrane that
connects the cell to the basement
membrane).
7. Exocytosis is the converse of endocytosis
and is the process by which most molecules
are secreted from the cell. Secreted
molecules are packaged in membrane
vesicles derived from the trans Golgi network
that fuse with the plasma membrane to
release their contents into the extracellular
milieu.
Chapter 3, Section 2
Basic Terminology
Figure 1: Receptor-mediated endocytosis & phagocytosis
8. Autophagy literally means “self eating” and is the cellular response to starvation by
which cells catabolize cellular contents to
provide the building blocks for essential
molecules such as amino acids. Put another
way, autophagy is a house-keeping process
that maintains cellular homeostasis through
recycling of nutrients and degradation of
damaged or aged cytoplasmic constituents
such as mitochondria.
9. Xenophagy. A form of autophagy in which
cells degrade intracellular microbes (viruses
and intracellular bacteria) and is sometimes
referred to as antimicrobial autophagy.
Compare the differences between
pinocytosis, receptor-mediated
endocytosis & phagocytosis
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Chapter 3, Section 2
Basic Terminology
Mini Quiz - Transport in intestinal epithelial cells
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Chapter 3, Section 3
Introduction to Vesicular Trafficking
Membrane-bound vesicles containing cargo
need to be moved around the cell to support
various processes, which include the uptake of extracellular particles and solutes,
communication with the extracellular
environment, and delivery of newly synthesized
molecules to their final destinations.
There are two major pathways that involve
vesicular trafficking: the secretory pathway
(exocytosis) and the endocytic pathway.
We will cover both separately in the following
sections.
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In a nutshell, the secretory pathway delivers
newly synthesized molecules to their proper
locations within the cell or outside of the cell,
while the endocytic pathway delivers
extracellular components to the inside of the
cell for lysosomal degradation (endocytosis,
phagocytosis, pinocytosis), or into the cell
and then back out of the cell (recycling and
transcytosis).
In the following sections, each trafficking
event is discussed in detail.
Chapter 3, Section 4
Endocytosis
The plasma membrane serves as a formidable
barrier to most molecules. While some small
molecules and lipophilic molecules may freely
diffuse across the plasma membrane to enter
the cell, other molecules need to be transported
across the membrane through a process that
begins with endocytosis. Endocytosis can be
non-specific as occurs in pinocytosis and
fluid-phase endocytosis, or highly specific,
involving receptors with specificity for a
particular molecule (receptor-mediated
endocytosis). More on this later. For a quick
review of the three modes of receptor-mediated
endocytosis, see Movie 1.
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Movie 1: Receptor Mediated Endocytosis
http://vod.med.wmich.edu/?vod=mol_2016_vesiculartrafficking1
Chapter 3, Section 5
Phagocytosis
You will learn more about phagocytosis and
phagocytes in the Foundations of Immunology
and Infectious Disease course. For now,
phagocytes are macrophages and neutrophils,
cells of the immune system, which contain
MANY different cell surface receptors that
capture specific cargo destined for
degradation in the lysosome. This makes
sense because the phagocytes exist to kill
pathogens (see Figures 3 and 4). In addition to
receptors that recognize common features of
pathogens, phagocytes express receptors that
allow them to bind to antibodies that are
bound to pathogens or their products (e.g.,
bacterial toxins). They also contain receptors
that allow them to bind to proteins called
complement that decorate the surface of a
pathogen.
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When a receptor is involved in the uptake of a
cargo, we refer to this as receptor-mediated
endocytosis and this is exactly what
phagocytosis entails. Cargo that is brought into
a phagocyte by the process of phagocytosis is
enclosed in a specialized endosome termed a
phagosome. The phagosome then fuses with
a lysosome to become a phagolysosome.
This brings the pathogen into direct contact
with degradative enzymes and reactive oxygen
species that destroy the pathogen. Some
bacterial pathogens, like Shigella dysenteriae
and Listeria monocytogenes, which cause
diarrhea, have found a way to prevent
phagosome fusion with lysosomes and can
escape the phagosome to enter the cytosol
where they can spread and cause disease.
Chapter 3, Section 5
Phagocytosis
Figure 3: Macrophage phagocytosis
A scanning electron micrograph of a mouse
macrophage phagocytosing two chemically
altered red blood cells. The pink arrows point
to edges of thin processes (pseudopods)
derived from the macrophage that are
extending as collars to engulf erythrocytes. (Image source: Jean Paul Revel.)
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Figure 4: Neutrophil Phagocytosis
An electron micrograph of a neutrophil phagocytosing a
bacterium, which is in the process of dividing. (Image source: Dorothy F. Bainton, Phagocytic Mechanisms in
Health and Disease. New York: Intercontinental Book
Corporation, 1971.)
Chapter 3, Section 6
Pinocytosis
All eukaryotic cells continually ingest
extracellular fluids and pieces of their plasma
membrane via pinocytosis. This is a
constitutive process (ongoing) in contrast to
phagocytosis, which is triggered by receptor
engagement. Pinocytosis brings in nutrients
and also allows for plasma membrane
turnover. When “old” membrane is removed by endocytosis, it is replaced by newly
synthesized membrane that is delivered to the
plasma membrane via exocytosis. See Movie 2 for an overview of pinocytosis.
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Movie 2: Pinocytosis
Chapter 3, Section 7
Clathrin-Coated Pits & Clathrin-Coated Vesicles
Endocytosis occurs at different sites on the
plasma membrane. Those regions containing
the protein clathrin are termed clathrincoated pits and the vesicles formed are termed
clathrin-coated vesicles (see Figures 5 & 6
and Movie 3). Clathrin also helps shape the
vesicles that derive from the endoplasmic
reticulum containing newly synthesized
proteins, and from the Golgi containing newly
glycosylated proteins. The clathrin coat is shed
shortly after vesicle formation and there are two major proteins termed coat proteins that
associate with clathrin-coated vesicles: COP I
and COP II. COP I facilitates movement of
vesicles from the Golgi to the rough ER, a
process termed retrograde trafficking, while
COP II facilitates movement of vesicles in the
other direction as occurs in the normal secretory
pathway (anterograde trafficking).
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Figure 5: Clathrin scaffolding
This electron micrograph shows the basketlike appearance of the clathrin scaffolding
Chapter 3, Section 7
Clathrin-Coated Pits & Clathrin-Coated Vesicles
Figure 6: Formation of a clathrin-coated vesicle from a clathrin-coated pit
These electron micrographs illustrate the probable sequence of events in the formation of a clathrin-coated
vesicle from a clathrin-coated pit. The clathrin-coated pits and vesicles shown are larger than those seen in
normal-sized cells. They are involved in taking up lipoprotein particles into a very large hen oocyte to form
yolk. The lipoprotein particles bound to their membrane-bound receptors can be seen as a dense, fuzzy layer on
the extracellular surface of the plasma membrane—which is the inside surface of the vesicle. (Image source:
M.M. Perry and A.B. Gilbert, J. Cell Sci. 39:257–272, 1979. © The Company of Biologists.)
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Chapter 3, Section 7
Clathrin-Coated Pits & Clathrin-Coated Vesicles
Movie 3: Clathrin-mediated Endocytosis
http://vod.med.wmich.edu/?vod=mol_2016_vesiculartrafficking2
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Chapter 3, Section 8
Caveolae
Endocytosis may also occur at regions of
the plasma membrane termed caveolae, which
contain the protein caveolin. Caveolae are rich
in cholesterol, glycosphingolipids and
glycosylphosphatidylinositol (GPI)-anchored
proteins. As discussed in Movie 4, caveolin
knockout mouse studies show that caveolae do
not have a major role in endocytosis or
transcytosis. Rather, caveolae are now thought
to provide structural support to cell
membranes.
Interestingly, ganglioside GM1 is found in
caveolae and provides a binding site for
cholera toxin! This is one mechanism by
which cholera toxin, produced by the
bacterium Vibrio cholerae, enters the
intestinal epithelial cell from the intestinal
lumen to cause the disease cholera.
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Experimentally, caveolae can be dissociated
from other regions of the plasma membrane
in nonionic detergents and because of their
high lipid content they float in sucrose
gradients where they can be collected and
studied. These regions of the membrane are
often referred to as lipid rafts because they
appear as floating rafts in the phospholipid
bilayer of the cell (see Figure 7 and Movie 4).
Chapter 3, Section 8
Caveolae
Figure 7: Caveolae
Click here for a description of the image below.
Click here for a description of the image above.
Regions of the plasma membrane containing the protein caveolin are termed caveolae.
(Image source: R.G.W. Anderson, from K.G. Rothberg et al., Cell 68:673–682, 1992. © Elsevier)
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Chapter 3, Section 8
Caveolae
Movie 4: Caveolin-mediated Endocytosis
http://vod.med.wmich.edu/?vod=mol_2016_vesiculartrafficking3
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Chapter 3, Section 9
Receptor-Mediated Endocytosis
Receptor-mediated endocytosis refers to
the uptake of macromolecules into the cell
following binding to transmembrane receptors
that are specific for individual cargo. So what
happens to cargo following receptor-mediated
endocytosis? In general, cargo bound to
transmembrane receptors in clathrin-coated pits are delivered to an early endosome
where, if they remain attached to their receptor,
they are recycled back out of the cell via a
recycling endosome or transported to the
opposite membrane via a transcytotic vesicle.
Alternatively, the cargo can dissociate from its
receptor and enter a late endosome, which
fuses with the lysosome where the cargo is
degraded. Whether the cargo remains attached
to its receptor in the acidic milieu of the early
endosome or not determines whether it is
recycled/transcytosed or degraded, respectively.
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Endosome membranes contain a hydrogen
pump called the vacuolar H+-ATPase that
pumps hydrogen ions into the vesicle lumen,
creating a pH of ~ 5-6. At this pH, most cargo
dissociate from their receptors and are
degraded in the lysosome while their
receptors are recycled back to the plasma
membrane for another round of cargo
loading. Some cargo remain associated with
their receptors in the early endosome and
have one of two fates: both cargo and receptor
are degraded, or the receptor transports the
cargo back to the plasma membrane where
the cargo is released (recycled in nonpolarized cells or transcytosed in polarized
cells).
Chapter 3, Section 9
Receptor-Mediated Endocytosis
In contrast to the fate of cargo that enter the
cell on receptors in clathrin-coated pits, cargo
brought in on receptors localized to caveolae
are retained on their receptor and delivered to
specialized endosomes termed transcytotic
vesicles that are targeted to the opposite
membrane of the cell in a process termed
transcytosis.
In addition to clathrin- and caveolinmediated endocytosis, a third pathway for
uptake into the cell exists termed clathrinand caveolin-independent endocytosis.
See Movie 5 to learn more about this
mechanism.
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Movie 5: Clathrin Caveolin-Independent
Endocytosis
http://vod.med.wmich.edu/?vod=mol_2016_vesiculartrafficking4
Chapter 3, Section 10
Recycling
A good example of a recycling receptor is the transferrin receptor, which binds to
transferrin, a soluble protein that carries iron
in the blood. Upon binding to transferrin, the
complex enters an early endosome where
exposure to low pH releases the iron. The
iron-free transferrin (apotransferrin) remains
associated with its receptor at acidic pH and is recycled back to the cell surface where at
the neutral pH of the extracellular fluid it
dissociates from its receptor and is free to pick
up more iron to begin the cycle again (see the
animation in Figure 8. You may also refer
back to Movie 4 to review transferrin receptor
trafficking).
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Figure 8: Animation of recycling
Chapter 3, Section 11
Transcytosis
Transcytosis, also termed transcellular
transport, refers to the delivery of cargo
across a polarized cell. A hallmark feature of
polarized cells is the division of their cell
surface into functionally distinct membrane
domains. As shown in Figure 9, the intestinal
epithelial cell (enterocyte) nicely demonstrates
cell polarity. Immunoglobulin A (IgA) is one of
the most important immunoglobulins in the
body as it defends mucosal surfaces against
pathogens and their products such as toxins.
We will cover this process in more detail in
Foundations of Immunology and Infectious
Disease, but for now let’s keep it simple.
26
Figure 9: Transcytosis
B cells produce IgA, which binds to the polymeric
immunoglobulin receptor at the basolateral membrane of
the intestinal epithelial cell. This receptor delivers IgA to a
series of endosomal compartments and ultimately to the
apical membrane where IgA is released onto the mucosal
surface of the intestine.
Chapter 3, Section 11
Transcytosis
Figure 10:
Dimeric IgA Transport Mediated by plgR
B cells in the intestine secrete IgA antibodies,
which are transported across the intestinal
epithelial cell by a receptor called the polymeric
immunoglobulin receptor (pIgR). This receptor
is localized to the basolateral aspect of the
intestinal epithelial cell membrane where it
binds to IgA and takes it into the cell through
the process of receptor-mediated
endocytosis. The pIgR-IgA complex remains
together and traffics across the cell where after
fusion with the apical membrane, IgA is released
from its receptor (transcytosis) (Figure 10).
Simplified drawing of pIgR-mediated dimeric IgA
transport across an intestinal epithelial cell.
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Chapter 3, Section 11
Review of Receptor-Mediated Endocytosis
Movie 6: Review of Receptor-Mediated Endocytosis
http://vod.med.wmich.edu/?vod=mol_2016_vesiculartrafficking5
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Chapter 3, Section 12
Exocytosis
Exocytosis is essentially the inverse of
endocytosis where intracellular vesicles fuse
with the plasma membrane and release their
cargo. In some cases, exocytosis delivers new
membrane components to the plasma
membrane and in other cases it serves to
release secretory material to the extracellular
space as part of the normal secretory pathway.
Both recycling and transcytotic vesicles
release cargo through the process of
exocytosis. To understand some of the basic
dynamics involved and for a nice review of
endocytosis and exocytosis, view the following
two movies.
29
Movie 7: Protein trafficking
https://www.youtube.com/watch?v=rvfvRgk0MfA
&list=PL954A470FA30AD66B&index=3
Chapter 3, Section 12
Exocytosis
Movie 8: Endocytosis and exocytosis
http://highered.mheducation.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/
dl/free/0072437316/120068/bio02.swf::Endocytosis+and+Exocytosis
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Chapter 3, Section 13
SNAREs & Rabs
Figure 11A: SNAREs - membrane fusion
How do vesicles know where to go? You can
now appreciate how crazy it is inside a cell
with multiple vesicular trafficking events
going on. How do the individual vesicles know
where to go?
The answer involves SNAREs and Rabs.
SNAREs are membrane-bound proteins that
provide specificity for vesicle targeting and
catalyze membrane fusion events. There are at
least 20 different types of SNAREs and each
associate with a different segment of the
secretory or endocytic pathway. Those
SNAREs associated with a vesicle are termed
v-SNAREs and those associated with the
target membrane are termed t-SNAREs. Vand t-SNAREs wrap around each other to
make a tight complex and in this way facilitate
membrane fusion (Figure 11A and 11B).
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Figure 11B: SNAREs - membrane fusion
http://www.nature.com/nature/journal/v438/
n7068/fig_tab/nature04397_F1.html
Chapter 3, Section 13
SNAREs & Rabs
Rabs are small GTP-binding proteins that
associate with the exterior of membrane
vesicles and regulate vesicle docking and
pairing of t- and v-SNAREs. There are over 60
different Rab proteins and they have various
locations in the cell, including endosomes,
recycling vesicles, lysosomes, etc. Upon
activation by binding to GTP, Rabs recruit
effector proteins (molecular motors, enzymes
and membrane fusion factors) to vesicle
membranes to facilitate vesicle docking to a
target membrane. Importantly, Rab proteins
are active in the GTP-bound form and when
GTP is hydrolyzed to GDP, Rabs become
inactive (Figure 12).
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Figure 12: Rabs: GTP-binding proteins
Chapter 3, Section 14
Lysosomes
The graveyard! Lysosomes are the primary
sites of intracellular degradation and the final
resting place for cargo that are neither recycled
nor transcytosed. They contain degradative
enzymes termed acid hydrolases (e.g., proteases,
nucleases, lipases, phosphatases and
glycosidases) that require an acidic environment
for optimal activity. A hydrogen ion pump,
termed the vaculoar H+-ATPase pump, allows
the lysosomes to reach a pH of about 5 (Figure
13).
There are 3 opportunities for material to enter
the lysosome (Figure 14). The first is from the
phagosome, which fuses with the lysosome to
form a phagolysosome. The second is from an
early endosome, which matures into a late
endosome and then a lysosome. The third
involves the process of autophagy.
To get a basic picture of lysosome biogenesis
and function, view Movie 9.
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Figure 13: H+-ATPase pump and
lysosome pH
Chapter 3, Section 14
Lysosomes
Movie 9: Lysosomes
Figure 14: Routes of lysosomes access
https://www.youtube.com/watch?v=ekdIEpSf-1I
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Chapter 3, Section 15
Autophagy & Xenophagy
Figure 15: Autophagy
Autophagy, as the name suggests, means
“self eating” and this is the way cells get rid
of old, damaged or senescent organelles such
as mitochondria. In this process, cytoplasmic
contents are sequestered in a unique doublemembrane structure termed the
autophagosome. Cytoplasmic cargo in
autophagosomes are degraded by fusion of
autophagosomes and lysosomes and
activation of the lysosomal degradation
pathway. Although autophagy is
fundamentally a 'self-eating' process, it also
facilitates degradation of pathogens through
a process termed xenophagy (xeno, the
prefix, means foreign) (see Figure 15).
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Exposed and defenseless: The parasite
Toxoplasma gondii, stripped of its
protective membrane, is enveloped by a
double-membrane sac and ready to be
consumed by lysosomes.
http://www.brown.edu/Administration/News_Bureau/
2006-07/06-014.html
Chapter 3, Section 16
Summary
Figure 16: Summary of Vesicular Trafficking
Study Figure 16 for a nice summary of vesicular
trafficking.
Note: it is not necessary to memorize the receptors and
ligands.
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Chapter 4
Assessment
Interactive Quiz
37
Chapter 5
To Learn More
Please visit the following websites if you wish to
learn more (optional):
1. Transport into the Cell from the Plasma
Membrane: Endocytosis
5. How Viruses Hijack Endocytic Machinery
http://www.ncbi.nlm.nih.gov/books/NBK26870/
2. Role of Rab GTPases in Membrane Traffic
and Cell Physiology
http://physrev.physiology.org/content/91/1/119
3. Membrane Traffic
https://www1.imperial.ac.uk/nhli/molecular/
membrane_traffic/
4. Rab proteins and Rab-associated proteins:
major actors in the mechanism of proteintrafficking disorders
http://www.ncbi.nlm.nih.gov/pmc/articles/
PMC2413085/
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http://www.nature.com/scitable/topicpage/howviruses-hijack-endocytic-machinery-14364991
6. Autophagy and bacterial infectious diseases
http://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3296818/
7. Eating the strangers within: host control of
intracellular bacteria via xenophagy.
http://www.ncbi.nlm.nih.gov/pubmed/21740500
Autophagy
Autophagy literally means “self eating” and is the cellular
response to starvation by which cells catabolize cellular content to
provide the building blocks for essential molecules such as amino
acids. Put another way, autophagy is a housekeeping process that
maintains cellular homeostasis through recycling of nutrients and
degradation of damaged or aged cytoplasmic constituents such as
mitochondria.
Related Glossary Terms
Drag related terms here
Index
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Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Lysosomes
Chapter 3 - Autophagy & Xenophagy
Cargo
Cargo refers to anything that can be taken into and transported
within a cell through the process of vesicular trafficking. Some
examples of cargoes are: hormones, immunoglobulins,
neurotransmitters, bacteria, viruses and apoptotic cells.
Related Glossary Terms
Drag related terms here
Index
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Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Introduction to Vesicular Trafficking
Chapter 3 - Phagocytosis
Chapter 3 - Receptor-Mediated Endocytosis
Chapter 3 - Transcytosis
Chapter 3 - Exocytosis
Chapter 3 - Lysosomes
Chapter 3 - Autophagy & Xenophagy
Endocytosis
Endocytosis refers to the uptake of cargo into a cell by
invagination of the plasma membrane and its internalization in an
endosome, a membrane-bound vesicle containing cargo for
sorting. There are three main forms of endocytosis: pinocytosis,
receptor-mediated endocytosis and phagocytosis.
Related Glossary Terms
Drag related terms here
Index
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Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Introduction to Vesicular Trafficking
Chapter 3 - Endocytosis
Chapter 3 - Pinocytosis
Chapter 3 - Clathrin-Coated Pits & Clathrin-Coated Vesicles
Chapter 3 - Caveolae
Chapter 3 - Exocytosis
Endosome
Endosome (or endocytic vesicle) is a membrane-bound vesicle
containing cargo for sorting.
Related Glossary Terms
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Chapter 3 - Basic Terminology
Chapter 3 - Phagocytosis
Chapter 3 - Receptor-Mediated Endocytosis
Chapter 3 - Receptor-Mediated Endocytosis
Chapter 3 - Receptor-Mediated Endocytosis
Chapter 3 - Recycling
Chapter 3 - Lysosomes
Exocytosis
Exocytosis is the converse of endocytosis and is the process by
which most molecules are secreted from the cell. These molecules
are packaged in membrane vesicles derived from the trans Golgi
network that fuse with the plasma membrane to release their
contents into the extracellular milieu.
Related Glossary Terms
Drag related terms here
Index
Find Term
Chapter 3 - Basic Terminology
Chapter 3 - Introduction to Vesicular Trafficking
Chapter 3 - Pinocytosis
Chapter 3 - Exocytosis
Lysosome
A lysosome is a specialized organelle containing hydrolytic
enzymes that degrades cargo.
Related Glossary Terms
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Index
Find Term
Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Phagocytosis
Chapter 3 - Receptor-Mediated Endocytosis
Chapter 3 - Lysosomes
Chapter 3 - Autophagy & Xenophagy
Phagocytosis
Phagocytosis (from Greek phagein, meaning to eat) is the
process by which particulate material, such microorganisms or
dead cells, is endocytosed by a cell. This largely occurs in immune
cells termed phagocytes (macrophages and neutrophils). Note that
the term “phagocyte” refers to a cell that performs phagocytosis.
Phagocytosis involves the uptake of particulate cargo into large
vesicles called phagosomes.
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Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Introduction to Vesicular Trafficking
Chapter 3 - Pinocytosis
Chapter 3 - Lysosomes
Phagosome
Phagosomes are large vesicles containing particulate cargo
acquired through the process of phagocytosis
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Chapter 3 - Basic Terminology
Chapter 3 - Phagocytosis
Pinocytosis
Pinocytosis is a form of endocytosis in which soluble materials
(fluids and solutes) are taken up from the extracellular
environment and incorporated into vesicles for digestion. Literally,
pinocytosis is “cell drinking.” Pinocytosis is also termed fluid-phase
endocytosis.
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Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Introduction to Vesicular Trafficking
Chapter 3 - Endocytosis
Chapter 3 - Pinocytosis
Receptor-mediated endocytosis
Receptor-mediated endocytosis, as the name suggests,
requires that a specific receptor bind to and transport a cargo into
the cell. Such transport receptors can be found associated with
specialized membrane domains rich in clathrin or caveolae
(discussed in the sections below).
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Chapter 3 - Basic Terminology
Chapter 3 - Basic Terminology
Chapter 3 - Endocytosis
Chapter 3 - Phagocytosis
Chapter 3 - Receptor-Mediated Endocytosis
Chapter 3 - Transcytosis
Recycling
Recycling is the process of returning cargo to the extracellular
milieu following its uptake into the cell.
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Chapter 3 - Basic Terminology
Chapter 3 - Introduction to Vesicular Trafficking
Chapter 3 - Recycling
Transcytosis
Transcytosis is the process from moving cargo that has been
taken into the cell and enclosed in an endosome from one pole of
the cell to the opposite pole.
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Chapter 3 - Basic Terminology
Chapter 3 - Introduction to Vesicular Trafficking
Chapter 3 - Receptor-Mediated Endocytosis
Chapter 3 - Transcytosis
Chapter 3 - Transcytosis
Xenophagy
A form of autophagy in which cells degrade intracellular microbes
(viruses and intracellular bacteria) is termed xenophagy and is
sometimes referred to as antibacterial autophagy.
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Chapter 3 - Basic Terminology
Chapter 3 - Autophagy & Xenophagy