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Molecular and Cellular Biology, April 2002, p. 2650-2662, Vol. 22, No. 8
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.8.2650-2662.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Nir2, a Novel Regulator of Cell Morphogenesis

Donghua Tian, Vladimir Litvak, Maria Toledo-Rodriguez, Shari Carmon, and Sima Lev*

Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel

Received 10 October 2001/ Returned for modification 9 November 2001/ Accepted 14 January 2002

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.


* Corresponding author. Mailing address: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel. Phone: 972-8-934-2126. Fax: 972-8-934-4131. E-mail: sima.lev{at}weizmann.ac.il.


Molecular and Cellular Biology, April 2002, p. 2650-2662, Vol. 22, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.8.2650-2662.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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