Scholarlink

<p>CAST is a core active zone scaffold protein, yet its role in Rab6-dependent trafficking remains unclear. Here, we identify the coiled-coil domain of CAST (CC10) as a direct Rab6-binding module and show that CAST selectively interacts with the GTP-bound form of Rab6 in both heterologous cells and neurons. Biochemical mapping, isothermal titration calorimetry, and bimolecular fluorescence complementation demonstrate that CC10 is necessary and sufficient for Rab6 recognition. In cultured hippocampal neurons, CAST promotes the presynaptic accumulation of Rab6, whereas CC10-disrupting mutations abolish this effect without detectably altering Rab6 distribution within axonal regions under our imaging conditions. These results define a CAST-dependent mechanism that spatially restricts Rab6 at presynaptic boutons, extending ELKS-based models of Rab6 cargo capture and providing a structural basis for the organization of presynaptic trafficking.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

CAST controls presynaptic sequestration of Rab6 in neurons

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月10日

查看全文
  • Yamato Hida,
  • Atsushi Shimada,
  • Yeon-Jeong Kim,
  • Miyuki Kato-Murayama,
  • Mikako Shirouzu,
  • Toshihisa Ohtsuka

摘要

CAST is a core active zone scaffold protein, yet its role in Rab6-dependent trafficking remains unclear. Here, we identify the coiled-coil domain of CAST (CC10) as a direct Rab6-binding module and show that CAST selectively interacts with the GTP-bound form of Rab6 in both heterologous cells and neurons. Biochemical mapping, isothermal titration calorimetry, and bimolecular fluorescence complementation demonstrate that CC10 is necessary and sufficient for Rab6 recognition. In cultured hippocampal neurons, CAST promotes the presynaptic accumulation of Rab6, whereas CC10-disrupting mutations abolish this effect without detectably altering Rab6 distribution within axonal regions under our imaging conditions. These results define a CAST-dependent mechanism that spatially restricts Rab6 at presynaptic boutons, extending ELKS-based models of Rab6 cargo capture and providing a structural basis for the organization of presynaptic trafficking.