脂肪细胞中Munc18c的缺失不影响胰岛素诱导的GLUT4转运(已撤稿2016-01-13)

动物脂肪和肌肉组织中葡萄糖的摄取是通过受胰岛素调控的GLUT4储存囊泡的运输实现的.Sec1p的同源物Munc18c被认为是通过控制SNARE复合物的装配来使GLUT4囊泡锚定到质膜上的重要物质.我们发现Munc18c的缺失没有影响GLUT4的转运上膜,也没有影响Syntaxin4在细胞膜上的定位.在缺少Munc18c和功能性Syntaxin2的时候,GLUT4的转运可能和Munc18b有关.在3T3-L1脂肪细胞中与Syntaxin4具有强烈相互作用的是Munc18c而不是Munc18a和Munc18b.然而,当缺少Munc18c时,Munc18a和Munc18b与Syntaxin4体现出较弱的相互作用.因此,Syntaxin4可能在胰岛素刺激GLUT4转运过程中起到重要的作用,且与SM蛋白的相互作用是有代偿性的.

Munc18c is Dispensable for Insulin-stimulated GLUT4 Translocation in Adipocytes(Retracted January 13, 2016)

The insulin-dependent uptake of glucose by adipose and muscle tissues is accomplished through the regulated vesicle trafficking of the GLUT4 glucose transporter to the plasma membrane. The Sec1p homologue Munc18c is believed to play a central role in the docking of GLUT4 vesicles by controlling SNARE complex assembly. In the present study we have examined the function of SM proteins in insulin-stimulated GLUT4 trafficking in adipocytes. Syntaxin4 at the plasma membrane is not dependent on the presence of Munc18c. We found that absence of Munc18c did not affect GLUT4 externalization at the plasma membrane and GLUT4 trafficking was normal in the absence of Munc18c and functional Syntaxin2, known to be associated with Munc18b. Syntaxin4 demonstrates a robust interaction with Munc18c but not either Munc18a or Munc18b in 3T3-L1 adipocytes. However, Munc18a and Munc18b exhibited weak interaction with Syntaxin4 in the background of absence of Munc18c. These data suggest that Syntaxin4 may play an important role in insulin-stimulated GLUT4 trafficking and its interaction with SM proteins are complementary.