Rab 3D in rat adipose cells and its overexpression in genetic obesity (Zucker fatty rat).
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.
Guerre-Millo
M
M
Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Baldini
G
G
Lodish
H F
HF
Lavau
M
M
Cushman
S W
SW
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D013347:Subcellular Fractions / Q000737:chemistry; D020692:rab3 GTP-Binding Proteins
D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins