Hanono Abraham, Garbett Damien, Reczek David, Chambers David N, Bretscher Anthony
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
J Cell Biol. 2006 Dec 4;175(5):803-13. doi: 10.1083/jcb.200604046.
EPI64 is a TBC domain-containing protein that binds the PDZ domains of EBP50, which binds ezrin, a major actin-binding protein of microvilli. High-resolution light microscopy revealed that ezrin and EBP50 localize exclusively to the membrane-surrounded region of microvilli, whereas EPI64 localizes to variable regions in the structures. Overexpressing EPI64 results in its and EBP50's relocalization to the base of microvilli, including to the actin rootlet devoid of ezrin or plasma membrane. Uncoupling EPI64's binding to EBP50, expression of any construct mislocalizing its TBC domain, or knock down of EBP50 results in loss of microvilli. The TBC domain of EPI64 binds directly to Arf6-GTP. Overexpressing the TBC domain increases Arf6-GTP levels, and expressing dominant-active Arf6 results in microvillar loss. These data reveal that microvilli have distinct cytoskeletal subdomains and that EPI64 regulates microvillar structure.
EPI64是一种含有TBC结构域的蛋白质，它与EBP50的PDZ结构域结合，而EBP50又与埃兹蛋白结合，埃兹蛋白是微绒毛的一种主要肌动蛋白结合蛋白。高分辨率光学显微镜显示，埃兹蛋白和EBP50仅定位于微绒毛的膜包围区域，而EPI64定位于这些结构中的可变区域。过表达EPI64会导致其自身以及EBP50重新定位于微绒毛基部，包括定位于没有埃兹蛋白或质膜的肌动蛋白小根。解除EPI64与EBP50的结合、任何使其TBC结构域定位错误的构建体的表达，或敲低EBP50都会导致微绒毛的丧失。EPI64的TBC结构域直接与Arf6-GTP结合。过表达TBC结构域会增加Arf6-GTP水平，而表达显性活性的Arf6会导致微绒毛丧失。这些数据表明，微绒毛具有不同的细胞骨架亚结构域，并且EPI64调节微绒毛结构。
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