RGD Reference Report - Nadrin, a novel neuron-specific GTPase-activating protein involved in regulated exocytosis. - Rat Genome Database

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Nadrin, a novel neuron-specific GTPase-activating protein involved in regulated exocytosis.

Authors: Harada, A  Furuta, B  Takeuchi, K  Itakura, M  Takahashi, M  Umeda, M 
Citation: Harada A, etal., J Biol Chem 2000 Nov 24;275(47):36885-91.
RGD ID: 633422
Pubmed: PMID:10967100   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M004069200   (Journal Full-text)

It has been proposed that the cortical actin filament networks act as a cortical barrier that must be reorganized to enable docking and fusion of the synaptic vesicles with the plasma membranes. We identified a novel neuron-associated developmentally regulated protein, designated as Nadrin. Expression of Nadrin is restricted to neurons and correlates well with the differentiation of neurons. Nadrin has a unique structure; it contains a GTPase-activating protein (GAP) domain for Rho family GTPases, a potential coiled-coil domain, and a succession of 29 glutamines. In vitro the GAP domain activates RhoA, Rac1, and Cdc42 GTPases. Expression of Nadrin in NIH3T3 cells markedly reduced the number of the actin stress fibers and the formation of the ruffled membranes, suggesting that Nadrin regulates actin filament reorganization. In PC12 cells, Nadrin colocalized with synaptotagmin in the neurite termini and also with cortical actin filaments in the subplasmalemmal regions. Expression of Nadrin or its mutant composed of the coiled-coil and GAP domain enhanced Ca(2+)-dependent exocytosis of PC12 cells, but a mutant lacking the GAP domain inhibited exocytosis. These results suggest that Nadrin plays a role in regulating Ca(2+)-dependent exocytosis, most likely by catalyzing GTPase activity of Rho family proteins and by inducing the reorganization of the cortical actin filaments.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
actin filament organization acts_upstream_of_or_withinIDA 633422PMID:10967100MGI 
calcium-ion regulated exocytosis acts_upstream_of_or_withinIDA 633422PMID:10967100MGI 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytoplasm located_inIDA 633422; 633422PMID:10967100MGI 

Objects Annotated

Genes (Rattus norvegicus)
Arhgap17  (Rho GTPase activating protein 17)
Syt1  (synaptotagmin 1)

Objects referenced in this article
Gene ARHGAP17 Rho GTPase activating protein 17 Homo sapiens
Gene Arhgap17 Rho GTPase activating protein 17 Mus musculus
Gene Myl3 myosin light chain 3 Rattus norvegicus

Additional Information