Disease relevance of Gdi1

• Furthermore, the Rab GDIalpha-deficient mice showed hypersensitivity to bicuculline, an inducer of epileptic seizures [1].
• All human neuroblastoma cell lines and tumor specimens examined express hu GDI alpha gene to various extents, while a human T cell leukemia cell line, MOLT3, does not [2].

Psychiatry related information on Gdi1

• Mice deficient for the synaptic vesicle protein Rab3a show impaired spatial reversal learning and increased explorative activity but none of the behavioral changes shown by mice deficient for the Rab3a regulator Gdi1 [3].
• The general similarity to human mental retardation is striking, and suggests that the Gdi1 mutants may provide insights into the human defect and into the molecular mechanisms important for development of cognitive functions [4].
• Gdi1-deficient mice are impaired in tasks requiring formation of short-term temporal associations, suggesting a defect in short-term memory [4].
• Deletion of the mental retardation gene Gdi1 impairs associative memory and alters social behavior in mice [4].

High impact information on Gdi1

• In Rab GDIalpha-deficient mice, synaptic potentials in the CA1 region of the hippocampus displayed larger enhancement during repetitive stimulation, which was apparently opposite to the phenotype of Rab3A-deficient mice [1].
• In mice, as in humans, lack of Gdi1 spares most central nervous system functions and preferentially impairs only a few forebrain functions required to form temporal associations [4].
• Targeted disruption of guanosine diphosphate-dissociation inhibitor for Rho-related proteins, GDID4: normal hematopoietic differentiation but subtle defect in superoxide production by macrophages derived from in vitro embryonal stem cell differentiation [5].
• Northern blot analysis revealed that hu GDI alpha gene is expressed abundantly in the brain but much less in other tissues, while hu GDI beta gene is ubiquitously expressed [2].
• These results suggest that hu GDI alpha gene expression is not related to the differentiation state of neuronal cells [2].

Biological context of Gdi1

• Such divergence in phenotypes implies that the putative synaptic interaction between Gdi1 and Rab3a should be reconsidered and re-analysed [3].
• Furthermore, we explored effects of specific genetic alterations (ERK1 gene deletion Gdi1 gene deletion) on this measure [6].

Anatomical context of Gdi1

• It has been recently recognized that at least two GDP dissociation inhibitor (GDI) isoforms, GDI-1 and GDI-2, can bind and release GDP-bound Rab proteins from membranes (Shisheva, A., Südhof, T.C., and Czech, M. P. (1994) Mol. Cell. Biol. 14, 3459-3468) [7].
• The present studies show that a strikingly higher level of GDI-2 fractionates with total membranes of COS-1 cells, Chinese hamster ovary cells, and 3T3-L1 adipocytes compared to GDI-1, which is virtually totally cytosolic [7].
• Previous work showed strikingly higher levels of GDI-2 than GDI-1 fractionate with total membranes of cultured cells and are visualized in the perinuclear region in 3T3-L1 adipocytes [8].

Regulatory relationships of Gdi1

• The goals of this study were to analyse possible behavioral consequences of the lack of synaptic plasticity in the mossy fiber pathway using a broad battery of sensitive behavioral measures that has been used previously to analyse the behavior of Gdi1 mice lacking a protein thought to regulate Rab3a [3].

Other interactions of Gdi1

• On the other hand, the phenotypic changes in the Rab3a(-/-) mice bore no relation to the behavioral changes as observed in the Gdi1 mice [3].

References