A novel rabconnectin‐3‐binding protein that directly binds a GDP/GTP exchange protein for Rab3A small G protein implicated in Ca<sup>2+</sup>‐dependent exocytosis of neurotransmitter

Kawabe, Hiroshi; Sakisaka, Toshiaki; Yasumi, Masato; Shingai, Tatsushi; Izumi, Genkichi; Nagano, Fumiko; Deguchi-Tawarada, Maki; Takeuchi, Masami; Nakanishi, Hiroyuki; Takai, Yoshimi

doi:10.1046/j.1365-2443.2003.00655.x

Cited by 51 publications

(61 citation statements)

References 23 publications

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“…Again, the Rab3A-regulated hub of the synapse provides the best validation of the approach. We observe tight coclustering of Rab3A with three distinct groups: 1) Rab regulators and effectors including GDI1(␣) (Sudhof, 2004), RIM3, Rabphilin-3A (Fukuda, 2003), calmodulin (Park et al, 1997), Synapsin (Syn1; Giovedi et al, 2004aGiovedi et al, , 2004b, Rab3 GEP-binding protein Rabconnectin-3 beta (Kawabe et al, 2003), and a potential RabGAP, RUTBC1 (Katoh, 2004); 2) SNARE system components including VAMP2, NSF (Chen and Scheller, 2001;Gerst, 2003;Sollner, 2003;Ungar and Hughson, 2003), Synaptotagmin I (Koh and Bellen, 2003), and Synaptophysin (Calakos and Scheller, 1994); and finally 3) coat machinery components AP3 2 (Hinners and Tooze, 2003), DNJC6/Auxilin, and Dynamin III (Lafer, 2002). Although Dynamin I has a broad tissue distribution and has a distinct clustering profile, the striking linkage of Dynamin III to Rab3A suggests a central, if not specialized, role in the synapse (Gray et al, 2003).…”

Section: The Membromementioning

confidence: 79%

“…For example, Rab3A clusters with HERC1 (Rosa et al, 1996) and the potential GEF Syn1 (Giovedi et al, 2004a). Although the Rab3A GEF Rab3GEP and GAP Rab3GAP have more divergent distributions suggestive of interaction with other Rab GTPases, the Rab3A-hub did contain the Rab3GEP-interacting protein Rabconnectin-3 beta (Kawabe et al, 2003), which may provide added specificity to Rab3A GEF recognition in vivo. As a second example, clustering of ALS2 (Otomo et al, 2003) with Rab5A; syntenin (Tomoda et al, 2004) with Rab5C; and RASA1, APPL1, and APPL2 (Miaczynska et al, 2004) with Rab5B ( Figure 2) is also in good agreement with well-established biochemical data and highlights potential strong differences in isoform activity in different tissues.…”

Section: Rab Regulators Rab Gtpases Do Not Function In Isolationmentioning

confidence: 99%

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Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Gürkan

Lapp

Alory

et al. 2005

MBoC

116

107

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Rab GTPases and SNARE fusion proteins direct cargo trafficking through the exocytic and endocytic pathways of eukaryotic cells. We have used steady state mRNA expression profiling and computational hierarchical clustering methods to generate a global overview of the distribution of Rabs, SNAREs, and coat machinery components, as well as their respective adaptors, effectors, and regulators in 79 human and 61 mouse nonredundant tissues. We now show that this systems biology approach can be used to define building blocks for membrane trafficking based on Rab-centric protein activity hubs. These Rab-regulated hubs provide a framework for an integrated coding system, the membrome network, which regulates the dynamics of the specialized membrane architecture of differentiated cells. The distribution of Rab-regulated hubs illustrates a number of facets that guides the overall organization of subcellular compartments of cells and tissues through the activity of dynamic protein interaction networks. An interactive website for exploring datasets comprising components of the Rab-regulated hubs that define the membrome of different cell and organ systems in both human and mouse is available at http://www.membrome.org/. INTRODUCTIONUnderstanding the molecular basis for the organization of the exocytic and endocytic membrane trafficking pathways in the eukaryotic cell remains a formidable challenge. The foundation of these pathways is the lipid bilayer that separates different subcellular compartments, their distinguishing features encoded by phospholipid composition, and unique sets of integral and peripheral membrane proteins. By harnessing and regulating the fundamental processes of membrane fission and fusion through the action of protein complexes, the lipid bilayer can be exploited to produce a variety of distinct subcellular compartments with unique chemical environments that play essential roles in cell and organ function. Moreover, it is now evident that these subcellular compartments are dynamic structures in continuous and specific communication through carrier vesicles and tubules that mobilize cargo to specific destinations. They can be disassembled and reassembled in a remarkably facile manner in response to cell signaling pathways, mitosis, or by simple chemical perturbants.Implicit in these dynamic pathways is the need to systematically and reversibly regulate protein interactions. Although traditional phylogenetic analyses provided significant insights into the diversity of components that direct membrane traffic (Pereira-Leal and Seabra, 2000;Chen and Scheller, 2001;Pereira-Leal and Seabra, 2001), our understanding of the basic cellular building blocks that organize this diversity into contiguous pathways is still fragmentary. Reductionist approaches using biochemical and molecular tools also provide important insights into specific steps of a pathway. However, understanding the global interconnectivities of complex biological pathways, such as cargo trafficking, will require new approaches utilizing modern ...

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Section: The Membromementioning

confidence: 79%

Section: Rab Regulators Rab Gtpases Do Not Function In Isolationmentioning

confidence: 99%

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Gürkan

Lapp

Alory

et al. 2005

MBoC

116

107

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“…Therefore, it is likely that the mutated protein of p130 lacking Rab3 GAP activity is expressed in the patients, whereas p130 is not expressed in our mice. This mutated protein could interact with various proteins, such as the noncatalytic subunit p150 (15), rabconnectin-3 (31,32), and the unidentified proteins as well as the intact protein. Another possibility is that this mutated p130 may suppress (or stimulate) the functions of these interacting proteins, resulting in the generation of abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Rab3 GTPase-activating protein regulates synaptic transmission and plasticity through the inactivation of Rab3

Sakane¹,

Manabe²,

Ishizaki

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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Rab3A small G protein is a member of the Rab family and is most abundant in the brain, where it is localized on synaptic vesicles. Evidence is accumulating that Rab3A plays a key role in neurotransmitter release and synaptic plasticity. Rab3A cycles between the GDP-bound inactive and GTP-bound active forms, and this change in activity is associated with the trafficking cycle of synaptic vesicles at nerve terminals. Rab3 GTPase-activating protein (GAP) stimulates the GTPase activity of Rab3A and is expected to determine the timing of the dissociation of Rab3A from synaptic vesicles, which may be coupled with synaptic vesicle exocytosis. Rab3 GAP consists of two subunits: the catalytic subunit p130 and the noncatalytic subunit p150. Recently, mutations in p130 were found to cause Warburg Micro syndrome with severe mental retardation. Here, we generated p130-deficient mice and found that the GTPbound form of Rab3A accumulated in the brain. Loss of p130 in mice resulted in inhibition of Ca 2؉ -dependent glutamate release from cerebrocortical synaptosomes and altered short-term plasticity in the hippocampal CA1 region. Thus, Rab3 GAP regulates synaptic transmission and plasticity by limiting the amount of the GTP-bound form of Rab3A.Rab3A ͉ Rab3 GAP p130 ͉ neurotransmitter release ͉ synaptic plasticity ͉ Warburg Micro syndrome

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“…One such class of mutants are those affecting the Rabconnectin-3 complex, a heterodimer of the proteins Rabconnectin-3α and Rabconnectin-3β (Rbcn-3A and Rbcn-3B in Drosophila) (Kawabe et al, 2003;Nagano et al, 2002). Preliminary data indicated that loss of Rbcn-3A in terminal cells leads to defects in terminal cell lumen formation (M.M.M.…”

Section: Identification Of Candidate Luminal Intermediates In Developmentioning

confidence: 99%

Intracellular lumen formation in Drosophila proceeds via a novel subcellular compartment

Nikolova

Metzstein

2015

Development

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Cellular tubes have diverse morphologies, including multicellular, unicellular and subcellular architectures. Subcellular tubes are found prominently within the vertebrate vasculature, the insect breathing system and the nematode excretory apparatus, but how such tubes form is poorly understood. To characterize the cellular mechanisms of subcellular tube formation, we have refined methods of high pressure freezing/freeze substitution to prepare Drosophila larvae for transmission electron microscopic (TEM) analysis. Using our methods, we have found that subcellular tube formation may proceed through a previously undescribed multimembrane intermediate composed of vesicles bound within a novel subcellular compartment. We have also developed correlative light/TEM procedures to identify labeled cells in TEM-fixed larval samples. Using this technique, we have found that Vacuolar ATPase (V-ATPase) and the V-ATPase regulator Rabconnectin-3 are required for subcellular tube formation, probably in a step resolving the intermediate compartment into a mature lumen. In general, our ultrastructural analysis methods could be useful for a wide range of cellular investigations in Drosophila larvae.

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A novel rabconnectin‐3‐binding protein that directly binds a GDP/GTP exchange protein for Rab3A small G protein implicated in Ca²⁺‐dependent exocytosis of neurotransmitter

Abstract: Background : Rab3A, a member of the Rab3 small G protein family, regulates Ca

Cited by 51 publications

References 23 publications

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Rab3 GTPase-activating protein regulates synaptic transmission and plasticity through the inactivation of Rab3

Intracellular lumen formation in Drosophila proceeds via a novel subcellular compartment

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A novel rabconnectin‐3‐binding protein that directly binds a GDP/GTP exchange protein for Rab3A small G protein implicated in Ca2+‐dependent exocytosis of neurotransmitter

Abstract: Background : Rab3A, a member of the Rab3 small G protein family, regulates Ca

Cited by 51 publications

References 23 publications

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Rab3 GTPase-activating protein regulates synaptic transmission and plasticity through the inactivation of Rab3

Intracellular lumen formation in Drosophila proceeds via a novel subcellular compartment

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Resources

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A novel rabconnectin‐3‐binding protein that directly binds a GDP/GTP exchange protein for Rab3A small G protein implicated in Ca²⁺‐dependent exocytosis of neurotransmitter