Multiple roles of auxilin and hsc70 in clathrin-mediated endocytosis.
The ATP-dependent dissociation of clathrin from clathrin-coated vesicles (CCVs) by the molecular chaperone Hsc70 requires J-domain cofactor proteins, either auxilin or cyclin-G-associated kinase (GAK). Both the nerve-specific auxilin and the ubiquitous GAK induce CCVs to bind to Hsc70. The removal of auxilin or GAK from various organisms and cells has provided definitive evidence that Hsc70 uncoats CCVs in vivo. In addition, evidence from various studies has suggested that Hsc70 and auxilin are involved in several other key processes that occur during clathrin-mediated endocytosis. First, Hsc70 and auxilin are required for the clathrin exchange that occurs during coated-pit invagination and constriction; this clathrin exchange may catalyze any rearrangement of the clathrin-coated pit (CCP) structure that is required during invagination and constriction. Second, Hsc70 and auxilin may chaperone clathrin after it dissociates from CCPs so that it does not aggregate in the cytosol. Third, auxilin and Hsc70 may be involved in the rebinding of clathrin to the plasma membrane to form new CCPs and independently appear to chaperone adaptor proteins so that they can also rebind to membranes to nucleate the formation of new CCPs. Finally, if formation of the curved clathrin coat induces membrane curvature, then Hsc70 and auxilin provide the energy for this curvature by inducing ATP-dependent clathrin exchange and rearrangement during endocytosis and ATP-dependent dissociation of clathrin at the end of the cycle so that it is energetically primed to rebind to the plasma membrane.
Eisenberg
Evan
E
Laboratory of Cell Biology, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892-0301, USA.
Greene
Lois E
LE
D000818:Animals; D034021:Auxilins / Q000737:chemistry / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D003034:Coated Pits, Cell-Membrane / Q000502:physiology; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000378:metabolism; D004705:Endocytosis; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D017434:Protein Structure, Tertiary
D034021:Auxilins; C534702:CCNG1 protein, human; D002966:Clathrin; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D050883:HSC70 Heat-Shock Proteins; D018832:Molecular Chaperones