amphiphysin

Amphiphysin is a family of adaptor proteins involved in endocytosis and membrane remodeling, with roles in synaptic vesicle recycling and intracellular membrane trafficking. The best-studied member, amphiphysin I, was identified in brain tissue as a phosphoprotein that binds dynamin and is implicated in synaptic vesicle endocytosis.

Structurally, amphiphysin family proteins typically contain an N-terminal BAR (BIN/amphiphysin/Rvs) domain that senses and can induce membrane curvature, followed by regions that mediate protein–protein interactions. A C-terminal SH3 domain in many family members binds proline-rich motifs in partner proteins such as dynamin, synaptojanin, and endophilin. Through SH3–proline interactions, amphiphysin can recruit dynamin to sites of endocytosis, coordinating membrane scission, while the BAR domain contributes to membrane shaping during vesicle formation.

Genetically, there are two main genes associated with amphiphysin activity: AMPH, encoding amphiphysin I, which is predominantly neuronal and involved in synaptic vesicle cycling; and BIN1, encoding amphiphysin II (also called BIN1 or amphiphysin II), which is more broadly expressed and generates multiple isoforms by alternative splicing. BIN1 participates in membrane remodeling beyond the nervous system, including roles in muscle T-tubule biogenesis; disruptions in BIN1 can cause centronuclear myopathy, and certain BIN1 isoforms are under study for other pathological contexts.

Clinical relevance includes autoantibodies against amphiphysin I in paraneoplastic neurological syndromes, most notably stiff-person syndrome associated with breast cancer. In genetics research, BIN1 has emerged as a risk locus in Alzheimer’s disease, with studies suggesting roles in endocytic trafficking and tau pathology, though the precise mechanisms remain under investigation. Overall, amphiphysin proteins act as essential links between membrane curvature and endocytic machinery across tissues.