Nir2, a novel regulator of cell morphogenesis.
Cell morphogenesis requires dynamic reorganization of the actin cytoskeleton, a process that is tightly regulated by the Rho family of small GTPases. These GTPases act as molecular switches by shuttling between their inactive GDP-bound and active GTP-bound forms. Here we show that Nir2, a novel protein related to Drosophila retinal degeneration B (RdgB), markedly affects cell morphology through a novel Rho-inhibitory domain (Rid) which resides in its N-terminal region. Rid exhibits sequence homology with the Rho-binding site of formin-homology (FH) proteins and leads to an apparent loss of F-actin staining when ectopically expressed in mammalian cells. We also show that Rid inhibits Rho-mediated stress fiber formation and lysophosphatidic acid-induced RhoA activation. Biochemical studies demonstrated that Nir2, via Rid, preferentially binds to the inactive GDP-bound form of the small GTPase Rho. Microinjection of antibodies against Nir2 into neuronal cells markedly attenuates neurite extension, whereas overexpression of Nir2 in these cells attenuates Rho-mediated neurite retraction. These results implicate Nir2 as a novel regulator of the small GTPase Rho in actin cytoskeleton reorganization and cell morphogenesis.
Tian
Donghua
D
Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
Litvak
Vladimir
V
Toledo-Rodriguez
Maria
M
Carmon
Shari
S
Lev
Sima
S
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D005136:Eye Proteins; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; C113505:PITPNM1 protein, human; C485161:Pitpnm protein, mouse; D011994:Recombinant Proteins; D020741:rho GTP-Binding Proteins