Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
Biochem Biophys Res Commun. 2010 Jan 15;391(3):1336-41. doi: 10.1016/j.bbrc.2009.12.045. Epub 2009 Dec 16.
SNARE proteins (VAMP2, syntaxin4, and SNAP23) have been thought to play a key role in GLUT4 trafficking by mediating the tethering, docking and subsequent fusion of GLUT4-containing vesicles with the plasma membrane. The precise functions of these proteins have remained elusive, however. We have now shown that depletion of the vesicle SNARE (v-SNARE) VAMP2 by RNA interference in 3T3-L1 adipocytes inhibited the fusion of GLUT4 vesicles with the plasma membrane but did not affect tethering of the vesicles to the membrane. In contrast, depletion of the target SNAREs (t-SNAREs) syntaxin4 or SNAP23 resulted in impairment of GLUT4 vesicle tethering to the plasma membrane. Our results indicate that the t-SNAREs syntaxin4 and SNAP23 are indispensable for the tethering of GLUT4 vesicles to the plasma membrane, whereas the v-SNARE VAMP2 is not required for this step but is essential for the subsequent fusion event.
SNARE 蛋白（VAMP2、syntaxin4 和 SNAP23）被认为在 GLUT4 转运中发挥关键作用，通过介导含 GLUT4 的囊泡与质膜的连接、对接和随后融合。然而，这些蛋白质的确切功能仍然难以捉摸。我们现在已经表明，在 3T3-L1 脂肪细胞中通过 RNA 干扰耗尽囊泡 SNARE（v-SNARE）VAMP2 会抑制 GLUT4 囊泡与质膜的融合，但不会影响囊泡与膜的连接。相比之下，耗尽靶 SNARE（t-SNARE）syntaxin4 或 SNAP23 会导致 GLUT4 囊泡与质膜的连接受损。我们的结果表明，t-SNAREs syntaxin4 和 SNAP23 对于 GLUT4 囊泡与质膜的连接是不可或缺的，而 v-SNARE VAMP2 对于这一步骤不是必需的，但对于随后的融合事件是必需的。
