rab3 is a small GTP-binding protein exclusively localized to synaptic vesicles.

Mollard, Gabriele Fischer von; Mignery, Gregory A.; Baumert, Marion; Perin, Mark S.; Hanson, T J; Burger, Peter; Jahn, Reinhard; Südhof, Thomas C.

doi:10.1073/pnas.87.5.1988

Cited by 424 publications

(194 citation statements)

References 40 publications

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“…Also in our hands, confirming previous results, 16 both proteins have shown a dot-like pattern of immunoreactivity especially evident in the granular layer of cerebellum, an area particularly rich in synapses. In neuroendocrine and endocrine cells Rab3A and rabphilin-3A are involved in processes of highly regulated exocytosis, 17,18 although their precise role still needs to be completely clarified. The extensive conservation of both proteins from Caenorhabditis elegans to vertebrates 19 implies that they play a critical role and is consistent with our finding of a similar expression in mouse, rat, and human.…”

Section: Discussionmentioning

confidence: 99%

Glomerular Podocytes Possess the Synaptic Vesicle Molecule Rab3A and Its Specific Effector Rabphilin-3a

Rastaldi

Armelloni

Berra

et al. 2003

The American Journal of Pathology

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Several recent studies have focused on similarities between glomerular podocytes and neurons because the two cells share a specialized cytoskeletal organization and several expression-restricted proteins, such as nephrin and synaptopodin. In neurons, the small guanosine triphosphatase Rab3A and its effector rabphilin-3A form a complex required for the correct docking of synaptic vesicles to their target membrane. Because rabphilin-3A binds in neurons to cytoskeletal proteins also important for podocyte homeostasis, and the complex rabphilin-3A-Rab3A has been demonstrated in neurons and neuroendocrine cells, the aim of our work was to investigate their possible expression and regulation in podocytes. Normal kidneys from mouse, rat, and human were studied by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction to evaluate the expression of Rab3A and rabphilin-3A. Double-staining immunohistochemistry and immunogold electron microscopy were then used to precisely localize the two proteins at the cellular and subcellular levels. Rab-3A and rabphilin-3A regulations in disease were then analyzed in growth hormone-transgenic mice, a well established model of focal and segmental glomerulosclerosis, and in human biopsies from proteinuric patients. Our results demonstrated that rabphilin-3A and Rab3A are present in normal mouse, rat, and human kidneys, with an exclusively glomerular expression and a comma-like pattern of positivity along the glomerular capillary wall, suggestive for podocyte staining. Co-localization of both molecules with synaptopodin confirmed their presence in podocytes. By immunogold electron microscopy both proteins were found around vesicles contained in podocyte foot processes. Their expression was increased in growth hormonetransgenic mice compared to their wild-type counterpart, and in a subset of biopsies from proteinuric patients. Our data, demonstrating the presence of two synaptic proteins in podocytes, further supports similarities between cytoskeletal and vesicular organization of podocytes and neurons. The altered expression observed in mouse and human proteinuric diseases suggests a possible role for these molecules in glomerulopathies. Glomerular podocytes, the last barrier of glomerular filtration, are highly specialized branched cells provided with interdigitating foot processes that externally cover the entire glomerular capillary surface. Recent advances in cell biology and genetics have expanded our knowledge about these cells, especially through the identification of several functionally important specific podocyte proteins. 1 Some of these proteins, such as nephrin, GLEPP-1 (glomerular epithelial protein-1), synaptopodin, and the amino acid transporters CAT3 (cationic amino acid transporter-3) and EAAT2 (excitatory amino acid transporter-2), have been found to be specifically shared by podocytes and neurons, 2-5 two process-bearing cells that, although derived from different embryological layers, have several features in common, 6 such as a hi...

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Section: Discussionmentioning

confidence: 99%

Glomerular Podocytes Possess the Synaptic Vesicle Molecule Rab3A and Its Specific Effector Rabphilin-3a

Rastaldi

Armelloni

Berra

et al. 2003

The American Journal of Pathology

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“…No single cell expresses all of the rab family members. However, there are many Rab proteins whose expressions are ubiquitous over a variety of tissues and cells, such as Rab 1,2,4,5,[6][7][8][9][10][11][12][13][14]18,20,22,24,28, and 30. 2 Expression of some Rab proteins are highly regulated depending on cell type (epithelial, mesenchymal, or endothelial) and specific phenotype (differentiation, activation, or polarization).…”

Section: Discussionmentioning

confidence: 99%

Expression and Localization of a Novel Rab Small G Protein (Rab38) in the Rat Lung

Osanai

Iguchi

Takahashi

et al. 2001

The American Journal of Pathology

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The Rab small G protein family participates in intracellular vesicle transport, including exocytosis and endocytosis. The cDNA encoding a novel Rab-related small G protein (Rab38) has been cloned from rat lung cDNA library and recorded in GenBank (accession no. M94043). However, the expression and localization of the protein in the lung remains primarily unknown. We produced polyhistidine-tagged recombinant Rab38 and a polyclonal antibody with a synthetic peptide. Immunohistochemistry demonstrated that the protein is specifically localized in alveolar type II cells and in bronchial epithelial cells. In situ hybridization using a digoxygenin-labeled RNA riboprobe clearly showed that the mRNA of the protein is localized in alveolar type II cells and bronchial epithelial cells, especially terminal airway epithelial cells. Western blot and reverse transcriptase-polymerase chain reaction showed distinct expression of the protein and mRNA in isolated alveolar type II cells, but not in alveolar macrophages. The native protein was predominantly hydrophobic and was enriched in a high-density vesicle fraction but was barely detectable in nuclear and lamellar body fractions in alveolar type II cells. Immunofluorescence cytochemistry performed on cultured alveolar type II cells showed that Rab38 distributed extensively in the cytoplasm with a distribution pattern similar to endoplasmic reticulum rather than other subcellular organelles. These results suggest that this novel rab small G protein (Rab38) mediates vesicular transport in terminal airway epithelium. Small GTP-binding proteins are a group of monomeric intracellular proteins that have GTP/GDP binding and GTPase activities, and mediate essential cell functions, including cell growth/differentiation, cytoskeletal configuration (cell movement, change of shape, and contraction and relaxation), and intracellular vesicle transport, including exocytosis and endocytosis. 1,2 The ras p21 was found first and was soon followed by several other proteins. Now, more than 50 members form a ras superfamily. They have highly conserved domains, contributing to interaction with guanine nucleotides, in organisms from yeast through mammals. Most of these proteins are prenylated at their carboxy termini and specific subsets are also modified by palmitoylation. The ras-related superfamily is now recognized as consisting of three major gene families (ras, rho, and rab) and other minor families.The rab family has more than 30 members, the largest number among small G proteins. The Rab proteins are known to localize to specific cell organelles, and are found in both membrane-bound and cytosolic forms. 2,3 Thus, they are believed to mediate intracellular vesicle transport among restricted intracellular compartments. Although current information in the sequence database indicates more than 30 members, there are few Rab proteins for which intracellular localization and function have been clarified.A novel cDNA has been cloned from the rat lung cDNA library encoding a rab-related small G protei...

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“…The vertebrate rab3A and rab3C molecules associate specifically with synaptic vesicles (Fischer von Mollard et al, 1990, 1994a. Similarly, C. elegans R AB-3 colocalized with synaptic vesicles.…”

Section: Rab-3 Colocalizes With Synaptic Vesiclesmentioning

confidence: 99%

“…We searched for other rab-3 homologs in the C. elegans genome to determine whether other isoforms were present in C. elegans, as is the case in vertebrates (Fischer von Mollard et al, 1990;Mizoguchi et al, 1990). Because we were unable to identify sequences that encode molecules similar to rab-3 by low-stringency hybridization (data not shown) or by analysis of available C. elegans genomic and EST sequence data, we resorted to PCR-based methods.…”

Section: Search For Additional C Elegans Rab Genes Failed To Identifmentioning

confidence: 99%

Caenorhabditis elegans rab-3Mutant Synapses Exhibit Impaired Function and Are Partially Depleted of Vesicles

et al. 1997

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Rab molecules regulate vesicular trafficking in many different exocytic and endocytic transport pathways in eukaryotic cells. In neurons, rab3 has been proposed to play a crucial role in regulating synaptic vesicle release. To elucidate the role of rab3 in synaptic transmission, we isolated and characterized Caenorhabditis elegans rab-3 mutants. Similar to the mouse rab3A mutants, these mutants survived and exhibited only mild behavioral abnormalities. In contrast to the mouse mutants, synaptic transmission was perturbed in these animals. Extracellular electrophysiological recordings revealed that synaptic transmission in the pharyngeal nervous system was impaired. Furthermore, rab-3 animals were resistant to the acetylcholinesterase inhibitor aldicarb, suggesting that cholinergic transmission was generally depressed. Last, synaptic vesicle populations were redistributed in rab-3 mutants. In motor neurons, vesicle populations at synapses were depleted to 40% of normal levels, whereas in intersynaptic regions of the axon, vesicle populations were elevated. On the basis of the morphological defects at neuromuscular junctions, we postulate that RAB-3 may regulate recruitment of vesicles to the active zone or sequestration of vesicles near release sites.

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rab3 is a small GTP-binding protein exclusively localized to synaptic vesicles.

Cited by 424 publications

References 40 publications

Glomerular Podocytes Possess the Synaptic Vesicle Molecule Rab3A and Its Specific Effector Rabphilin-3a

Glomerular Podocytes Possess the Synaptic Vesicle Molecule Rab3A and Its Specific Effector Rabphilin-3a

Expression and Localization of a Novel Rab Small G Protein (Rab38) in the Rat Lung

Caenorhabditis elegans rab-3Mutant Synapses Exhibit Impaired Function and Are Partially Depleted of Vesicles

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