Xu Dalu, Hay Jesse C
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
J Cell Biol. 2004 Dec 20;167(6):997-1003. doi: 10.1083/jcb.200408135.
What is the first membrane fusion step in the secretory pathway? In mammals, transport vesicles coated with coat complex (COP) II deliver secretory cargo to vesicular tubular clusters (VTCs) that ferry cargo from endoplasmic reticulum exit sites to the Golgi stack. However, the precise origin of VTCs and the membrane fusion step(s) involved have remained experimentally intractable. Here, we document in vitro direct tethering and SNARE-dependent fusion of endoplasmic reticulum-derived COPII transport vesicles to form larger cargo containers. The assembly did not require detectable Golgi membranes, preexisting VTCs, or COPI function. Therefore, COPII vesicles appear to contain all of the machinery to initiate VTC biogenesis via homotypic fusion. However, COPI function enhanced VTC assembly, and early VTCs acquired specific Golgi components by heterotypic fusion with Golgi-derived COPI vesicles.
分泌途径中的第一个膜融合步骤是什么？在哺乳动物中，包被有包被复合体（COP）II的运输小泡将分泌性货物运送到囊泡管状簇（VTC），这些簇将货物从内质网出口位点运送到高尔基体堆栈。然而，VTC的确切起源以及所涉及的膜融合步骤在实验上仍然难以解决。在这里，我们记录了内质网衍生的COPII运输小泡在体外的直接拴系和SNARE依赖性融合，以形成更大的货物容器。该组装不需要可检测到的高尔基体膜、预先存在的VTC或COPI功能。因此，COPII小泡似乎包含通过同型融合启动VTC生物发生的所有机制。然而，COPI功能增强了VTC组装，并且早期VTC通过与高尔基体衍生的COPI小泡的异型融合获得了特定的高尔基体成分。
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