Amphiphysin Autoimmunity in Breast Cancer and Stiff-Man Syndrome.
Annual rept. 30 Sep 94-29 Sep 95,
YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE
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Amphiphysin, a neuronal protein first identified in chicken synaptic membranes, is the autoantigen of Stiff-Man Syndrome SMS associated with breast cancer. We have now cloned human amphiphysin and found the N-and C-terminal domains of the protein to be highly conserved between chicken and human. Patient autoantibodies have a distinct pattern of reactivity with amphiphysin, and the dominant autoepitope is located in its C-terminal region, which contains an SH3 domain. Portions of chicken and human amphiphysin are also homologous to portions of Rvs 167 and Rvs 161, two yeast proteins which are involved in cell entry into stationary phase upon exposure to unfavourable growth conditions.We have also demonstrated a specific, S113 domain-mediated, interaction between amphiphysin and dynamin by gel overlay and affinity chromatography. In addition, we show that the two proteins are colocalized in nerve terminals and are coprecipitated from brain extracts consistent with their interactions in situ. We also report that a region of amphiphysin distinct from its SH3 domain mediates its binding to the ccc subunit of AP2 adaptin, which is also concentrated in nerve terminals. These findings support a role of amphiphysin in synaptic vesicle endocytosis.
- Medicine and Medical Research
- Anatomy and Physiology