Turning CALM into excitement: AP180 and CALM in endocytosis and disease.
Dynamic flux of membrane between intracellular compartments is a key feature of all eukaryotic cells. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) play a crucial role in membrane dynamics by facilitating membrane fusion, for example at synapses where small synaptic vesicles (SVs) undergo activity-regulated neuroexocytosis, followed by the endocytic re-cycling of SV proteins and lipids. Recent work shows that the assembly protein 180 (AP180) N-terminal homology (ANTH) domain containing proteins AP180 and clathrin assembly lymphoid myeloid leukaemia (CALM) not only regulate the assembly of the endocytic machinery but also act as sorters for a subset of SNAREs, the vesicle-associated membrane proteins (VAMPs), most notably VAMP/synaptobrevin 2 at synapses. In this review, we summarise the current state of knowledge about the roles of AP180 and CALM family members in clathrin-dependent membrane traffic, the molecular mechanistic basis for their activities and their potential involvement in human disease.
Leibniz Institute for Molecular Pharmacology, 13125 Berlin, Germany.
Tanja
T
Maritzen
Seong Joo
SJ
Koo
Volker
V
Haucke
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion; D051379:Mice; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism*; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism
D002966:Clathrin; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human; D050600:SNARE Proteins; D050988:Vesicle-Associated Membrane Protein 2; C439023:clathrin assembly protein AP180