P022
Calcium binding protein 7 (CaBP7) functions in lysosomal
trafficking and mitosis via PI4KIIIβ
Dayani Rajamanoharan, Robert D. Burgoyne and
Lee P. Haynes
University of Liverpool, Liverpool, UK
Calcium Binding Proteins (CaBPs) are a subfamily of the
calmodulin- superfamily of EF hand containing calcium sensing
proteins. CaBPs can be further divided into 2 subgroups (CaBPs
1-5 and CaBPs 7/8) based on evolutionary relatedness stemming
from unique sequence features. CaBP7 and 8 have been shown
to interact with Phosphatidylinositol 4-Kinase-IIIbeta (PI4KIIIβ)
and to be involved in Golgi-to plasma membrane traffic. At
resting Ca2+ levels CaBP7/8 interact with PI4KIIIβ and inhibit
its enzymatic activity, whereas at high Ca2+ levels a second
Ca2+-binding protein NCS-1, displaces CaBP7/8 and stimulates
PI4KIIIβ activity. CaBP7 was identified in a high-throughput RNAi
screen as an essential protein during mitosis in mammalian cells.
Upon knock down of CaBP7 a 3-fold increase of binucleate cells
compared to control cells was observed. The same effect was
seen with PI4KIIIβ overexpression suggesting a role for CaBP7 in
regulating PI4KIIIβ during cytokinesis perhaps on lysosomes. We
present novel data showing that CaBP7 switches from a Golgi
associated localization in interphase cells to an almost entirely
lysosomal localization during mitosis. Intriguingly, we also show
that lysosomes redistribute to either side of the intercellular bridge
at cytokinesis. The link between CaBP7, PI4KIIIβ activity, phosphatidylinositol 4-phosphate levels and lysosomal function during
cytokinesis is of importance to our complete understanding of the
regulatory mechanisms controlling cell division.