Role of Rab GDP dissociation inhibitor α in regulating plasticity of hippocampal neurotransmission

Ishizaki, Hiroki; Miyoshi, Jun; Kamiya, Haruyuki; Togawa, Atsushi; Tanaka, Miki; Sasaki, Takuya; Endo, Kaori; Mizoguchi, Akira; Ozawa, Seiji; Takai, Yoshimi

doi:10.1073/pnas.97.21.11587

Cited by 74 publications

(59 citation statements)

References 23 publications

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“…The production of GDI-1 protein is critical for vesicular membrane transport in both the endocytic and also exocytic pathways via regulation of Ras-like GTPases of the Rab family proteins (Pfeffer et al, 1995;Martinez and Goud, 1998;Luan et al, 1999;Seabra et al, 2002). Moreover, GDI-1 has an important role in vivo to suppress hyperexcitability of the CA1 pyramidal neurons, which changes the firing properties of the neurons (Ishizaki et al, 2000). Consistent with previous reports demonstrating that MK-801 and memantine stimulate hypothalamic-puituitaryadrenal activity by activating corticotropin-releasing factor or cortocoliberin (CRF) in the hypothalamus (Lee et al, 1994;Zhou et al, 1998), we found the increased transcript levels of CRF after both treatments.…”

Section: Discussionmentioning

confidence: 99%

Identification of Genes Regulated by Memantine and MK-801 in Adult Rat Brain by cDNA Microarray Analysis

Marvanová

Lakso

Wong

2004

Neuropsychopharmacol

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In this study, we monitored gene expression profiles using cDNA microarrays after an acute systemic administration of the high affinity N-methyl-D-aspartate (NMDA) uncompetitive antagonist MK-801 (1 mg/kg; 4 h), and the clinically used moderate affinity antagonist memantine (25 mg/kg; 4 h) in adult rat brains. From a microarray containing 1090 known genes, 13 genes were regulated by both treatments of which 12 were upregulated and one was downregulated. In addition, 28 and 34 genes were regulated (X1.5-or p0.67-fold change) by either memantine or MK-801, respectively. Genes commonly regulated by both treatments and not previously reported were confirmed by in situ hybridization (ISH) and include regenerating liver inhibitory factor-1 (RL/IF-1), GDP-dissociation inhibitor 1 (GDI-1), neural visinin Ca 2 þ -binding protein 2 (NVP-2), neuromedin B receptor, and Na þ /K þ transporting ATPase 2b. ISH with memantine (5-50 mg/kg) revealed regulation of these genes in other cortical and hippocampal regions. RL/IF-1 induction occurred at 1 h and returned to basal levels by 8 h, consistent with the profile of an immediate early gene. Western blot analysis showed increases (B30-65%) 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. Genes regulated by a 5 mg/kg dose of memantine might be important in its therapeutic effects. These findings increase the number of known, differentially altered genes after treatment of uncompetitive NMDA receptor antagonists and suggest broader actions of these agents than previously realized.

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Section: Discussionmentioning

confidence: 99%

Identification of Genes Regulated by Memantine and MK-801 in Adult Rat Brain by cDNA Microarray Analysis

Marvanová

Lakso

Wong

2004

Neuropsychopharmacol

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“…56 RabGDIa-deficient mice revealed a role for this protein in neurotransmitter release and synaptic activity in the hippocampus. 57 More recently, D'Adamo et al 58 have produced a mouse model deficient for Gdi1 and showed that the lack of Gdi1 has an effect on the distribution of Rab4 and Rab5 pools, which are Rab proteins involved in synaptic vesicle exocytosis and that GDI deficiency is associated with a defect in short-term memory. Implication in the regulation of synaptic activity was also proposed for IL1RAP, another X-linked gene involved in MR.…”

Section: Synaptic Structure and Function And Mental Retardationmentioning

confidence: 99%

Genetics and pathophysiology of mental retardation

et al. 2006

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Mental retardation (MR) is defined as an overall intelligence quotient lower than 70, associated with functional deficit in adaptive behavior, such as daily-living skills, social skills and communication. Affecting 1-3% of the population and resulting from extraordinary heterogeneous environmental, chromosomal and monogenic causes, MR represents one of the most difficult challenges faced today by clinician and geneticists. Detailed analysis of the Online Mendelian Inheritance in Man database and literature searches revealed more than a thousand entries for MR, and more than 290 genes involved in clinical phenotypes or syndromes, metabolic or neurological disorders characterized by MR. We estimate that many more MR genes remain to be identified. The purpose of this review is to provide an overview on the remarkable progress achieved over the last decade in delineating genetic causes of MR, and to highlight the emerging biological and cellular processes and pathways underlying pathogeneses of human cognitive disorders.

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“…83 In addition, Rab GDIα has an important in Rab3A recycling to suppress hyperexcitability through modulation of presynaptic forms of plasticity in the hippocampus. 84 In the NAc, increased phosphorylation of Rab GDIα may serve as a compensatory mechanism to offset hyperexcitability induced by ionotropic glutamate receptors and increased phosphorylation of NR1 following cocaine self-administration in primates. 24 …”

Section: Cell Signalingmentioning

confidence: 99%

Integrative proteomic analysis of the nucleus accumbens in rhesus monkeys following cocaine self-administration

2008

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The reinforcing effects and long-term consequences of cocaine self-administration have been associated with brain regions of the mesolimbic dopamine pathway, namely the nucleus accumbens (NAc). Studies of cocaine-induced biochemical adaptations in rodent models have advanced our knowledge; however, unbiased detailed assessments of intracellular alterations in the primate brain are scarce, yet essential, to develop a comprehensive understanding of cocaine addiction. To this end, two-dimensional difference in gel electrophoresis (2D-DIGE) was used to compare changes in cytosolic protein abundance in the NAc between rhesus monkeys selfadministering cocaine and controls. Following image normalization, spots with significantly differential image intensities (P < 0.05) were identified, excised, trypsin digested and analyzed by matrix-assisted laser-desorption ionization time-of-flight time-of-flight (MALDI-TOF-TOF). In total, 1098 spots were subjected to statistical analysis with 22 spots found to be differentially abundant of which 18 proteins were positively identified by mass spectrometry. In addition, approximately 1000 protein spots were constitutively expressed of which 21 proteins were positively identified by mass spectrometry. Increased levels of proteins in the cocaine-exposed monkeys include glial fibrillary acidic protein, syntaxin-binding protein 3, protein kinase C isoform, adenylate kinase isoenzyme 5 and mitochondrial-related proteins, whereas decreased levels of proteins included β-soluble N-ethylmaleimide-sensitive factor attachment protein and neural and non-neural enolase. Using a complimentary proteomics approach, the differential expression of phosphorylated proteins in the cytosolic fraction of these subjects was examined. Two-dimensional gel electrophoresis (2DGE) was followed by gel staining with Pro-Q Diamond phosphoprotein gel stain, enabling differentiation of approximately 150 phosphoprotein spots between the groups. Following excision and trypsin digestions, MALDI-TOF-TOF was used to confirm the identity of 15 cocaine-altered phosphoproteins. Significant increased levels were detected for γ-aminobutyric acid type A receptor-associated protein 1, 14-3-3 γ-protein, glutathione S-transferase and brain-type aldolase, whereas significant decreases were observed for β-actin, Rab GDP-dissociation inhibitor, guanine deaminase, peroxiredoxin 2 isoform b and Results from these studies indicate coordinated dysregulation of proteins related to cell structure, signaling, metabolism and mitochondrial function. These data extend and compliment previous studies of cocaine-induced biochemical alterations in human post-mortem brain tissue, using an animal model that closely recapitulates the human condition and provide new insight into the molecular basis of the disease and potential targets for pharmacotherapeutic intervention.

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Role of Rab GDP dissociation inhibitor α in regulating plasticity of hippocampal neurotransmission

Cited by 74 publications

References 23 publications

Identification of Genes Regulated by Memantine and MK-801 in Adult Rat Brain by cDNA Microarray Analysis

Identification of Genes Regulated by Memantine and MK-801 in Adult Rat Brain by cDNA Microarray Analysis

Genetics and pathophysiology of mental retardation

Integrative proteomic analysis of the nucleus accumbens in rhesus monkeys following cocaine self-administration

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