Amphiphysin I and regulation of synaptic vesicle endocytosis.
Amphiphysin I, known as a major dynamin-binding partner localized on the collars of nascent vesicles, plays a key role in clathrin-mediated endocytosis (CME) of synaptic vesicles. Amphiphysin I mediates the invagination and fission steps of synaptic vesicles by sensing or facilitating membrane curvature and stimulating the GTPase activity of dynamin. Amphiphysin I may form a homodimer by itself or a heterodimer with amphiphysin II in vivo. Both amphiphysin I and II function as multilinker proteins in the clathrin-coated complex. Under normal physiological conditions, the functions of amphiphysin I and some other endocytic proteins are known to be regulated by phosphorylation and dephosphorylation. During hyperexcited conditions, the most recent data showed that amphiphysin I is truncated by the ca2-dependent protease calpain. Overexpression of the truncated form of amphiphysin I inhibited transferrin uptake and synaptic vesicle endocytosis (SVE). This suggests that amphiphysin I may be an important regulator for SVE when massive amounts of Ca2 flow into presynaptic terminals, a phenomenon observed in neurodegenerative disorders such as ischemia/anoxia, epilepsy, stroke, trauma and Alzheimer's disease. This review describes current knowledge regarding the general properties and functions of amphiphysin I as well as the functional regulations such as phosphorylation and proteolysis in nerve terminals.
Wu
Yumei
Y
Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Matsui
Hideki
H
Tomizawa
Kazuhito
K
D000199:Actins / Q000378:metabolism; D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013572:Synaptic Vesicles / Q000378:metabolism*
D000199:Actins; D033962:Adaptor Protein Complex 2; D048868:Adaptor Proteins, Signal Transducing; D002966:Clathrin; D009419:Nerve Tissue Proteins; C107640:SH3GL2 protein, human; C075637:amphiphysin; C097702:synaptojanin; D019703:Calcineurin; D010744:Phosphoric Monoester Hydrolases; D010739:Phospholipase D; D002154:Calpain