Amphiphysin I and regulation of synaptic vesicle endocytosis.

Abstract

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.

• Authors: Yumei Wu, Hideki Matsui, Kazuhito Tomizawa
• Journal: Acta medica Okayama (Acta Med Okayama) Vol. 63 Issue 6 Pg. 305-23 (Dec 2009) ISSN: 0386-300X [Print] Japan
• PMID: 20035287 (Publication Type: Journal Article, Review)

Chemical References

• Actins
• Adaptor Protein Complex 2
• Adaptor Proteins, Signal Transducing
• Clathrin
• Nerve Tissue Proteins
• SH3GL2 protein, human
• amphiphysin
• synaptojanin
• Calcineurin
• Phosphoric Monoester Hydrolases
• Phospholipase D
• Calpain

Topics

• Actins (metabolism)
• Adaptor Protein Complex 2 (metabolism)
• Adaptor Proteins, Signal Transducing (metabolism)
• Alternative Splicing
• Animals
• Calcineurin (metabolism)
• Calpain (metabolism)
• Cell Membrane (metabolism)
• Clathrin (metabolism)
• Endocytosis (physiology)
• Humans
• Nerve Tissue Proteins (genetics, metabolism)
• Phospholipase D (metabolism)
• Phosphoric Monoester Hydrolases (metabolism)
• Protein Structure, Tertiary
• Synaptic Vesicles (metabolism)