AMPHIPHYSIN-II (SH3P9 BIN1), A MEMBER OF THE AMPHIPHYSIN RVS FAMILY, IS CONCENTRATED IN THE CORTICAL CYTOMATRIX OF AXON INITIAL SEGMENTS AND NODES OF RANVIER IN BRAIN AND AROUND T-TUBULES IN SKELETAL-MUSCLE/

Amphiphysin (amphiphysin I), a dominant autoantigen in paraneoplastic Stiff-man syndrome, is a neuronal protein highly concentrated in nerve termin nals, where it has a putative role in endocytosis. The yeast h omologue of amphiphysin, Rvs167, has pleiotropic functions, including a role in endocytosis and in actin dynamics, suggesting that amphiphys in may also be implicated in the function of the presynaptic actin cyt oskeleton. We report here the characterization of a second mammalian a mphiphysin gene, amphiphysin II (SH3P9; BIN1), which encodes products primarily expressed in skeletal muscle and brain, as differentially sp liced isoforms. In skeletal muscle, amphiphysin II is concentrated aro und T tubules, while in brain it is concentrated in the cytomatrix ben eath the plasmamembrane of axon initial segments and nodes of Ranvier. In both these locations, amphiphysin II is colocalized with splice va riants of ankyrin3 (ankyrin(G)), a component of the actin cytomatrix. In the same regions, the presence of clathrin has been reported. These findings support the hypothesis that, even in mammalian cells, amphip hysin/Rvs family members have a role both in endocytosis and in actin function and suggest that distinct amphiphysin isoforms contribute to define distinct domains of the cortical cytoplasm. Since amphiphysin I I (BIN1) was reported to interact with Myc, it may also be implicated in a signaling pathway linking the cortical cytoplasm to nuclear funct ion.