Disease relevance of GDI1

• Molecular study of the PAK3 and GDI1 genes in nonsyndromic X-linked mental retardation spanish patients [1].

Psychiatry related information on GDI1

• Mutations in GDI1 are responsible for X-linked non-specific mental retardation [2].

High impact information on GDI1

• GDP dissociation inhibitor (GDI) is a general and essential regulator of Rab recycling that extracts prenylated Rab proteins from membranes at the end of their cycle of activity and facilitates their delivery to the donor membranes [3].
• Our results indicate that GDI1 plays a central role in the regulation of signal transduction cascades mediated by Rho GTPases [4].
• Cells lacking GDI1 are multinucleate, grow slowly and display a moderate pinocytosis defect, but rates of phagocytosis are unaffected [4].
• A large family (MRX48) with a nonspecific X-linked mental retardation condition is described [5].
• In addition to the nonsense mutation recently reported in MRX48, we have identified a novel missense mutation in exon 11 of the GDIalpha gene in one familial form of non-specific mental retardation [6].

Biological context of GDI1

• All 11 exons and splice junctions of the GDI1 gene were PCR-amplified and sequenced directly or screened by single-strand conformation analysis [7].
• GDP dissociation inhibitor prevents intrinsic and GTPase activating protein-stimulated GTP hydrolysis by the Rac GTP-binding protein [8].
• GDP dissociation inhibitor D4-GDI (Rho-GDI 2), but not the homologous rho-GDI 1, is cleaved by caspase-3 during drug-induced apoptosis [9].
• It was found that, similar to several other genes from the region, XAP-4 is split into exons of average size, which are interrupted by very short introns [10].
• We report on a family in which nonsyndromal mild to moderate mental retardation segregates as an X-linked trait (MRX41) [11].

Anatomical context of GDI1

• In the infected cells RhoA was dissociated from guanine nucleotide dissociation inhibitor-1 (GDI-1) and accumulated as a monomeric protein in the cytosol, whereas Rac and CDC42Hs remained GDI-bound [12].

Associations of GDI1 with chemical compounds

• Rho guanosine diphosphate-dissociation inhibitor plays a negative modulatory role in glucose-stimulated insulin secretion [13].
• Western blot analysis showed increases (approximately 30-65%) in GDI-1 protein present in both cytosolic and membrane fractions that were significant in the 84-kDa Rab bound form, suggesting that memantine influences Ras-like GTPase function [14].

Physical interactions of GDI1

• PRA1 inhibits the extraction of membrane-bound rab GTPase by GDI1 [15].

Other interactions of GDI1

• Therefore, GLUD2 and GDI1 can be excluded as candidate genes for this syndrome [7].
• GDI1 localized to GGA1pter and SLC6A8 to a mid-sized microchromosome [16].
• While the mammalian rab GDI beta-genes are ubiquitously expressed, the rab GDI alpha genes are predominantly expressed in neural tissues [17].
• However, very little is known with regard to potential regulation by G-protein regulatory factors (e.g., the guanosine diphosphate-dissociation inhibitor [GDI]) of insulin secretion from the islet beta-cell [13].
• Evolutionary conservation and genomic organization of XAP-4, an Xq28 located gene coding for a human rab GDP-dissociation inhibitor (GDI) [10].

Analytical, diagnostic and therapeutic context of GDI1

• The Northern blot analysis and in situ hybridization to sections of mouse embryos and postnatal tissues have revealed that the rab GDI alpha/XAP-4 is expressed predominantly in neural and sensory tissues and may thus serve a specific function in neural signal transmission [18].

References