Guerre-Millo M, Baldini G, Lodish H F, Lavau M, Cushman S W
Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Biochem J. 1997 Jan 1;321 ( Pt 1)(Pt 1):89-93. doi: 10.1042/bj3210089.
Members of the Rab 3 subfamily of low-molecular-mass GTP-binding proteins have been functionally implicated in regulated exocytosis. The aim of the present study was to examine the subcellular distribution of a member of this family, Rab 3D, in rat adipose cells, given the hypothesis that this protein might be involved in insulin-stimulated GLUT4 exocytosis. We show that Rab 3D immunoreactivity is associated predominantly with the high-density microsomal fraction, where the signal intensity is 3- and 7-fold greater than that in plasma membranes and low-density microsomes respectively. Rab 3D does not co-localize with GLUT4 on immuno-isolated intracellular vesicles and, unlike GLUT4, it is not redistributed in response to insulin. Thus, if Rab 3D plays a role in GLUT4 trafficking, it relies on mechanisms independent of relocation. We observed that Rab 3D is overexpressed in adipose cells of obese (fa/fa) Zucker rats, in a tissue- and isoform-specific manner. The pathophysiological significance of this defect remains elusive. This could form the molecular basis for altered adipose secretory function in obesity.
低分子量GTP结合蛋白Rab 3亚家族的成员在调节性胞吐作用中具有功能相关性。鉴于该蛋白可能参与胰岛素刺激的GLUT4胞吐作用这一假设，本研究的目的是检测该家族成员Rab 3D在大鼠脂肪细胞中的亚细胞分布。我们发现Rab 3D免疫反应性主要与高密度微粒体部分相关，其信号强度分别比质膜和低密度微粒体中的信号强度高3倍和7倍。Rab 3D在免疫分离的细胞内囊泡上不与GLUT4共定位，并且与GLUT4不同，它不会因胰岛素而重新分布。因此，如果Rab 3D在GLUT4转运中起作用，它依赖于独立于重新定位的机制。我们观察到Rab 3D在肥胖（fa/fa） Zucker大鼠的脂肪细胞中以组织和异构体特异性方式过表达。这种缺陷的病理生理学意义仍然难以捉摸。这可能构成肥胖中脂肪分泌功能改变的分子基础。
