Regulation of cell polarity and protrusion formation by targeting RhoA for degradation.
The Rho family of small guanosine triphosphatases regulates actin cytoskeleton dynamics that underlie cellular functions such as cell shape changes, migration, and polarity. We found that Smurf1, a HECT domain E3 ubiquitin ligase, regulated cell polarity and protrusive activity and was required to maintain the transformed morphology and motility of a tumor cell. Atypical protein kinase C zeta (PKCzeta), 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.
Wang
Hong-Rui
HR
Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M56 1x5, Canada.
Zhang
Yue
Y
Ozdamar
Barish
B
Ogunjimi
Abiodun A
AA
Alexandrova
Evguenia
E
Thomsen
Gerald H
GH
Wrana
Jeffrey L
JL
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement; D016764:Cell Polarity; D048429:Cell Size; D002471:Cell Transformation, Neoplastic; D003599:Cytoskeleton / Q000648:ultrastructure; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D034741:RNA, Small Interfering; D015398:Signal Transduction; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D020662:Guanine Nucleotide Exchange Factors; D011493:Protein Kinase C; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D000099221:Protein Kinase C zeta; C471641:SMURF2 protein, human; C492381:Smurf1 protein, mouse