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Cell surface dynamics, and the role of endocytic machineries
All cells are surrounded by a lipid plasma membrane that control transit of molecules into and out of the
cell through receptors and channels exposed on this cell surface. During endocytosis, distinct protein
machineries (coats) re-sculpture the plasma membrane into vesicular carriers that enclose molecules that
are to be taken up into the cell. Besides the canonical clathrin coated endocytic machinery, it is becoming
increasingly clear that additional membrane carriers such as caveolae and CLICs support the uptake of a
variety of molecules, including cellular receptors, membranes and infectious agents. We are studying the
proteins and mechanisms that are required to re-sculpture the plasma membrane into highly curved
tubular and vesicular structures with the following overall aims:
1. To identify and characterize the coat
proteins and mechanisms that facilitate the
formation of caveolae and CLICs and clarify
how the coat components influence the
dynamics of these membrane invaginations.
2. To understand how endocytic membranes
can serve as membrane reservoirs for
balancing membrane integrity and provide
protection
against
infectious
agents
mechanical and chemical stress.
Clathrin independent carriers (CLICs).
CLICs constitute a major endocytic pathway for rapid turnover of the cell surface and abundant uptake
of GPI-linked receptors, galectins, membranes, fluid, virus and bacterial toxins. This novel pathway is
very dynamic and accounts for a major part of the endocytosed material in fibroblasts. Uptake is
orchestrated by the small G-protein cdc42, which cooperates with GRAF1, Arf1 and ARHGAP10 to
control carrier formation (For review see (Mayor S et al. Cold Spring Harb Perspect Biol. 2014).
Caveolae
Caveolae are 50 nm invaginations of the plasma membrane enriched in cholesterol, sphingolipids and
the protein caveolin. Such invaginations are very abundant in certain tissues such as endothelium, fat and
smooth muscle and they are thought to play important roles in the control of lipid homeostasis, membrane
tension and endocytosis. Caveolae dysfunction is strongly associated with accelerated tumourigenesis,
cardiovascular disease, lipodystrophy, muscular dystrophy and diabetes. Caveolae biogenesis and
dynamics is regulated by a recently discovered coat protein complex and the regulatory proteins EHD2
and Pacsin2 (For review see (Parton and del Pozo, Nat Rev Mol Cell Biol. 2013)
Clathrin-coated vesicles
Clathrin-mediated endocytosis is used by all eukaryotic cells and provide uptake of versatile cargoes by
specific sorting into clathrin-coated vesicles. The clathrin endocytic machinery is composed of over 25
different protein components that bud off vesicles with a fixed size and rigid coat (For review see
(McMahon and Boucrot, Nat Rev Mol Cell Biol. 2011)