Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells.

Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells.
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DOI:
10.1038/ncb2541
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发表时间:
2012-08
影响因子:
21.3
通讯作者:
--
中科院分区:
生物学1区
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上皮组织的形成既需要产生顶底极性,又需要相邻细胞之间这种极性的协调以形成中央管腔。在从头形成管腔的过程中,矢量膜运输有助于形成单个顶膜,导致每个细胞仅对单个管腔做出贡献。在这里,通过对 3D 上皮结构所需基因的功能筛选,我们确定了突触结合蛋白样蛋白 2-a 和 4-a (Slp2-a/4-a) 在每个细胞单个顶端表面生成中的关键作用。 Slp2-a 以 PI(4,5)P2 依赖性方式定位于管腔膜,它靶向负载 Rab27 的囊泡以启动单个管腔。囊泡束缚和融合由 Slp4-a 以及 Rab27/Rab3/Rab8 和 SNARE Syntaxin-3 控制。 Slp2-a/4-a 共同协调矢量顶端运输的时空组织,以确保每个细胞仅发生单个顶端表面,从而形成单个管腔。
The formation of epithelial tissues requires both the generation of apical-basal polarity and the co-ordination of this polarity between neighboring cells to form a central lumen. During de novo lumen formation, vectorial membrane transport contributes to formation of a singular apical membrane, resulting in contribution of each cell to only a single lumen. Here, from a functional screen for genes required for 3D epithelial architecture we identify key roles for Synaptotagmin-like proteins 2-a and 4-a (Slp2-a/4-a) in generation of a single apical surface per cell. Slp2-a localizes to the luminal membrane in a PI(4,5)P2-dependent manner, where it targets Rab27-loaded vesicles to initiate a single lumen. Vesicle tethering and fusion is controlled by Slp4-a, in conjunction with Rab27/Rab3/Rab8 and the SNARE Syntaxin-3. Together, Slp2-a/4-a co-ordinate the spatiotemporal organization of vectorial apical transport to ensure only a single apical surface, and thus formation of a single lumen, occurs per cell.
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