Disease relevance of GDI2

• Reduction of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down syndrome brain [1].

High impact information on GDI2

• Differential intracellular localizations of GDP dissociation inhibitor isoforms. Insulin-dependent redistribution of GDP dissociation inhibitor-2 in 3T3-L1 adipocytes [2].
• Concomitantly, GLUT4 but not GDI-2 protein content of plasma membranes increased, suggesting release of GDI-2 into the cytoplasm in response to insulin [2].
• Insulin acutely decreased both GLUT4 and GDI-2 protein levels in the low density microsomes by about 50% [2].
• In 3T3-L1 adipocytes, most of the membrane-bound GDI-2 was present in a low density, intracellular membrane fraction [2].
• While the mammalian rab GDI beta-genes are ubiquitously expressed, the rab GDI alpha genes are predominantly expressed in neural tissues [3].

Biological context of GDI2

• The human rab GDI beta gene with long retroposon-rich introns maps to 10p15 and its pseudogene to 7p11-p13 [4].
• To further test whether the endogenous GDI-2 can adopt a gain-of-function conformation, we pharmacologically stimulated intact 3T3-L1 adipocytes to induce GDI-2 tyrosine phosphorylation [5].
• In this study we have addressed a plausible general activity of GDI-2 in supporting Rab membrane release and have analyzed the requirements of sequence-conserved vs variable regions of GDI-2 in these functional interactions [5].
• Here we report that GDI-2-containing structural elements are concentrated predominantly in the pericentriolar area in interphase CHO-T cells and differentiated 3T3-L1 adipocytes based on colocalization of GDI-2 and the centrosomal marker pericentrin [6].

Anatomical context of GDI2

• Together, these results indicate that (a) GDI-2 displays a general activity to release Rabs from membranes, (b) GDI-2-conserved residues, but not the C-terminal variable region, are essential for this activity, and (c) structural modifications in GDI-2 can enhance its functional activity, directing selective interactions with individual Rabs [5].
• During mitotic resolution of the centrosome into two identifiable foci in CHO-T cells, GDI-2 containing structures remain intact and also resolve into two regions surrounding the centrosome [6].
• The integrity of pericentriolar GDI-2-binding elements was not disrupted by either brief Triton X-100 extraction or microtubule cytoskeletal disassembly, achieved with nocodazole [6].
• Expressed c-Myc-tagged GDI-2 in transfected COS-7 cells targets to the same region [6].

Associations of GDI2 with chemical compounds

• Dissociation of pericentriolar GDI-2 from the Golgi markers beta-COP and lectin receptors was apparent upon brefeldin A treatment of 3T3-L1 adipocytes or CHO-T cells [6].

Enzymatic interactions of GDI2

• We found a pronounced increase of the Rab4 soluble form and its soluble complexes with the tyrosine-phosphorylated GDI-2 [5].

Analytical, diagnostic and therapeutic context of GDI2

• Localization of both GDI-2 and GLUT4 in the same perinuclear regions of these cells was established by immunofluorescence microscopy, whereas GDI-1 displayed a diffuse, cytoplasmic distribution [2].

References