脂肪细胞中Munc18c的缺失不影响胰岛素诱导的GLUT4转运

Munc18c is Dispensable for Insulin-stimulated GLUT4 Translocation in Adipocytes

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.

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 Sec1 p homologue Munc18 c 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 Munc18 c. We found that absence of Munc18 c did not affect GLUT4 externalization at the plasma membrane and GLUT4 trafficking was normal in the absence of Munc18 c and functional Syntaxin2, known to be associated with Munc18 b. Syntaxin4 demonstrates a robust interaction with Munc18 c but not either Munc18 a or Munc18 b in3T3-L1 adipocytes. However, Munc18 a and Munc18 b exhibited weak interaction with Syntaxin4 in the background of absence of Munc18 c. These data suggest that Syntaxin4 may play an important role in insulin-stimulated GLUT4 trafficking and its interaction with SM proteins are complementary.