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© The Rockefeller University Press, 0021-9525/1997//1355 $5.00
The Journal of Cell Biology, Volume 137, Number 6, , 1997 1355-1367

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

Department of Cell Biology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510

Amphiphysin (amphiphysin I), a dominant autoantigen in paraneoplastic Stiff-man syndrome, is a neuronal protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. The yeast homologue of amphiphysin, Rvs167, has pleiotropic functions, including a role in endocytosis and in actin dynamics, suggesting that amphiphysin may also be implicated in the function of the presynaptic actin cytoskeleton. We report here the characterization of a second mammalian amphiphysin gene, amphiphysin II (SH3P9; BIN1), which encodes products primarily expressed in skeletal muscle and brain, as differentially spliced isoforms. In skeletal muscle, amphiphysin II is concentrated around T tubules, while in brain it is concentrated in the cytomatrix beneath the plasmamembrane of axon initial segments and nodes of Ranvier. In both these locations, amphiphysin II is colocalized with splice variants 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, amphiphysin/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 II (BIN1) was reported to interact with Myc, it may also be implicated in a signaling pathway linking the cortical cytoplasm to nuclear function.

Please address all correspondence to Pietro De Camilli, Department of Cell Biology and HHMI, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510. Tel.: (203) 737-4465; Fax: (203) 7371762; E-mail: pietro.decamilli{at}yale.edu

Detlev Grabs' current address is Institut für Anatomie and Spezielle Embryologie, Universität Fribourg, 1 Rue Gockel, CH-1700 Fribourg, Switzerland.

Ottavio Cremona's permanent address is Department of Medical Sciences, II Faculty of Medicine, University of Torino, Via Solaroli 17, 21100 Novara, Italy.

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