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PMID:10967100

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Citation

Harada, A, Furuta, B, Takeuchi, K, Itakura, M, Takahashi, M and Umeda, M (2000) Nadrin, a novel neuron-specific GTPase-activating protein involved in regulated exocytosis. J. Biol. Chem. 275:36885-91

Abstract

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.

Links

PubMed Online version:10.1074/jbc.M004069200

Keywords

Actins/metabolism; Amino Acid Sequence; Animals; Brain/growth & development; Brain/metabolism; Calcium-Binding Proteins; Cloning, Molecular; Exocytosis; GTPase-Activating Proteins/chemistry; GTPase-Activating Proteins/genetics; GTPase-Activating Proteins/physiology; Gene Expression Regulation, Developmental; Membrane Glycoproteins/metabolism; Microscopy, Fluorescence; Molecular Sequence Data; Nerve Tissue Proteins/metabolism; Neurons/physiology; PC12 Cells; Rats; Synaptotagmins; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:SYT1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:RHG17

acts_upstream_of_or_within

GO:0017156: calcium-ion regulated exocytosis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:RHG17

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:RHG17

acts_upstream_of_or_within

GO:0007015: actin filament organization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:SYT1

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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