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Regulation of Cell Polarity and Protrusion Formation by Targeting RhoA for Degradation
Hong-Rui Wang,*,1Yue Zhang,*,1Barish Ozdamar,1,2Abiodun A. Ogunjimi,1Evguenia Alexandrova,3Gerald H. Thomsen,3Jeffrey L. Wrana1,2
The Rho family of small guanosine triphosphatases regulatesactin cytoskeleton dynamics that underlie cellular functionssuch as cell shape changes, migration, and polarity. We foundthat Smurf1, a HECT domain E3 ubiquitin ligase, regulated cellpolarity and protrusive activity and was required to maintainthe transformed morphology and motility of a tumor cell. Atypicalprotein kinase C zeta (PKC), an effector of the Cdc42/Rac1-PAR6polarity complex, recruited Smurf1 to cellular protrusions,where it controlled the local level of RhoA. Smurf1 thus linksthe polarity complex to degradation of RhoA in lamellipodiaand filopodia to prevent RhoA signaling during dynamic membranemovements.
1 Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M56 1x5, Canada. 2 Department of Medical Genetics and Microbiology, University of Toronto, Toronto M5S 1A8, Canada. 3 Department of Biochemistry and Cell Biology, Center for Developmental Genetics, CMM 348, Stony Brook University, Stony Brook, NY 11794–5215, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: wrana{at}mshri.on.ca
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), an effector of the Cdc42/Rac1-PAR6 polarity complex, recruited Smurf1 to cellular protrusions, where it controlled the local level of RhoA. Smurf1 thus links the polarity complex to degradation of RhoA in lamellipodia and filopodia to prevent RhoA signaling during dynamic membrane movements. 
To whom correspondence should be addressed. E-mail: 
