MEMBRANE DYNAMICS IN ENDOCYTOSIS
EUROCONFERENCE
Membrane Dynamics in Endocytosis: Structure-Function Relationship
Aghia Pelaghia, Crete, Greece, 10-15 September 1999
1. INTRODUCTION
Endocytosis (uptake of membrane and extracellular materials by invaginations of the
plasma membrane to form a small membrane-bounded vesicle) is a basic necessity
of all cells and is responsible for important physiological functions ranging from
acquisition of essential nutrients, cell signaling and synaptic function to cellular
defense and antigen presentation. The endocytic pathway is also exploited by a large
number of bacterial, viral and protozoan pathogens to gain entry to their host cells.
The molecules that control endocytosis as well as the structure, function and
interaction of endocytic compartments are key issues in contemporary cell biology
and are in general highly relevant to the wider fields of membrane transport,
organelle interaction and protein sorting, and cellular communication.
At the meeting, the structures and molecular mechanisms underlying endocytic
function as well as endocytosis in relation to health and disease were discussed. The
meeting aimed to provide a European forum through which laboratories involved in
the study of endocytosis and related fields could present their data, through which
collaborations could be established and through which younger scientists could
interact with established investigators.
2. REPORT
In the first part of the meeting focus was on the structures and molecular
mechanisms responsible for the formation of endocytic vesicles from the plasma
membrane. It was obvious that much new and important information has recently be
obtained on the structure and function of clathrin and associated molecules. Thus in
addition to e.g. impressive data regarding the structure of clathrin (a fibrous protein
that with the aid of assembly proteins polymerizes into a latice-like network at specific
regions on the cytosolic side of a membrane, thereby forming a clathrin-coated pit,
which buds off to form a vesicle) at very high resolution, the present state of art was
presented with respect to dynamin, adaptors and caveolins (d., a., and c. are all
molecules involved in the formation of clathrin-coated and other types of
invaginations and vesicles). Also the role of clathrin and associated molecules in
specialized cell types such as neurons was touched upon. Important data and
thoughts concerning the forces driving membrane curvature were presented.
Thereafter followed a number of talks describing the organization of the endocytic
apparatus, in particular with respect to the earlier steps in the downstream endocytic
trafficking (the intracellular transport routes and stations exploited by endocytosed
membrane and other material). A role for dynamin in the recycling of the transferrin
receptor from endosomes to the plasma membrane was reported, and also the role
of phosphatidylinositol 3-phosphate (a member of a group of molecules regulating
1
various cellular activities) and of endosome (a vesicle formed by fusions of endocytic
vesicles) lipid domains in endocytic membrane trafficking was highlighted. This part
of the meeting also included a talk on endocytic sorting of lipids and proteins.
Another study dealt with endocytic uptake and trafficking through endosomes
towards the trans-Golgi network (the last sorting station of the Golgi apparatus on the
secretory pathway) analysed by the use of plant and bacterial toxins. Finally new
data on the regulation of an alternative form of endocytosis, macropinocytosis (a
special type of endocytosis leading to the formation of large endocytic vesicles) ,
were presented. Then the focus shifted towards the role of the cytoskeleton (actin
and myosins) in endocytic events, a topic that has recently received considerably
interest.
The focus of the conference was then directed towards the late steps of endocytic
trafficking, and a new role of the GTPase Rab7 (a member of a large family of GTPbinding proteins regulating endocytic trafficking) in late endosome-lysosome fusion
and lysosome biogenesis (the process of formation of the last station on the
endocytic pathway, the lysosomes) was presented. The role of adaptors and signals
involved in the targeting to lysosomes weas analysed and interesting pathological
aspects of lipid transport to lysosomes and lysosomal degradation was presented.
After the above-mentioned analysis of endocytic uptake mechanisms and
downstream endocytic trafficking in general, a number of interesting talks dealt with
entry and intracellular processing of bacteria and vira. And finally some new,
important aspects of endocytosis in the kidney tubules mediated by a new member of
the LDL (Low Density Lipoprotein) receptor family, megalin (a member of the LDL
family), as well as the role of endocytosis in dendritic cells (a special cell type
involved in antigen presentation), was presented, the latter topic making a clear
connection to immunologi.
In conclusion, it was clear from the conference that membrane traffic has moved to
the center stage in modern cell biology. Various < classical > disciplines such as
molecular biology, biochemistry and structural cell biology (including various electron
microscopical techniques and confocal immunofluorescence microscopy (a special
form for optical microscopy)) are being brought together to yield a synergistic effect
more evident in this field than in any other field of contemporary cell biology. Also it
was obvious from the meeting that an increasing amount of information from other
fields (microbiology, immunology, pathology, developmental biology etc.) will be
found under the headings of membrane traffic/endocytic trafficking in the future.
The series of endocytosis meetings has become a major international event in the
membrane traffic field, as well as in the wider field of cell biology. This series of
meetings has proven its importance for the European scientific community. Not least
young European scientists (including several from less privileged areas) have
benefited from the meetings, made new connections, heard about job possibilities
etc. In addition, more senior investigators had an excellent opportunity to continue
the never-ending discussions on several important topics, and they were brought into
contact with the upcoming generation of young, very good and enthusiastic scientists
within the field of membrane traffic, not least during the poster sessions. Also,
selected young scientists gave very good oral presentations, some of them even for
the first time. All this has also been evident from the very nice responses received
after the meeting, both from young participants and senior people (including invited
speakers).
It must therefore be concluded that this series of conferences should continue,
hopefully with the support from the European Community. One improvement future
organizers should consider is to include even more young speakers (selected among
the applicants) in the programme.
2
ORGANISATIONAL AND ADMINISTRATIVE ASPECTS
The organization of the meeting and the involvement of the Office in Strasbourg has
been terrific. It is worth stressing that without this competent and enthusiastic team of
people, it would not be possible to organize this type of meetings in the same smooth
and professional way. I am grateful for the support from the European Commission
EuroConference activity of the Training & Mobility of Researchers (TMR)
Programme.
Bo van Deurs, Chairman.
3
Identification:
Scientist in charge:
LIFndocyt980378
Address:
1) The Panum Institute, Structural Cell Biology Unit,
Department of Medical Anatomy, Blegdamsvej 3, 2200
Copenhagen, Denmark
2) Institut Pasteur, Unité de Biologie des Interactions
Cellulaires, 25 rue du Dr. Roux, 75724 Paris Cedex 15,
France
Tel.:
Fax:
E-mail:
Contractor:
1) (45) 35 32 72 79 / 2) (33) 1 45 68 85 74
Contract n°:
ERBFMMACT 980378
1) VAN DEURS Bo
2) DAUTRY-VARSAT Alice
1) (45) 35 32 72 85 / 2) (33) 1 40 61 32 38
1) [email protected] / 2) [email protected]
HENDEKOVIC Josip
EURESCO Conferences, European Science
Foundation, 1 quai Lezay-Marnésia, 67080 Strasbourg
cedex, France
Tel. +33 (0)388 76 71 35
Fax. +33 (0) 388 36 69 87
E-Mail: [email protected]
Publications:
The following publication has resulted from the first conference: Traffic Report: "Membrane
Dynamics in Endocytosis: Structure-Function Relationship", by Raluca Gagescu, Jean
Gruenberg and Elizabeth Smythe, Traffic 1:84-88, 2000. Here a detailed outline of the
scientific aspects of the conference can be found.
It is also available on the Internet at: http://www.traffic.dk
www site:
- for events:
http://www.esf.org/euresco/99/LC99057A.HTM
http://www.esf.org/euresco/01/lc01057a.htm
- of contractor:
- other relevant:
http://www.esf.org/euresco
PROGRAMME OF EVENTS
Event n°1:
Event n°2:
Structure-function relationship Molecular regulation.
Dates:
10/09/99- 15/09/99 - 5 day
Dates:
06/10/01-11/10/01 - 5 day
Place:
Place:
Aghia pelaghia, Crete, Greece Tomar, Portugal.
TMR Home Page
CORDIS
Programme Home Pages
4