Polarized trafficking of E-cadherin is regulated by Rac1 and Cdc42 in Madin-Darby canine kidney cells.
E-cadherin is a major cell-cell adhesion protein of epithelia that is trafficked to the basolateral cell surface in a polarized fashion. The exact post-Golgi route and regulation of E-cadherin transport have not been fully described. The Rho GTPases Cdc42 and Rac1 have been implicated in many cell functions, including the exocytic trafficking of other proteins in polarized epithelial cells. These Rho family proteins are also associated with the cadherin-catenin complexes at the cell surface. We have used functional mutants of Rac1 and Cdc42 and inactivating toxins to demonstrate specific roles for both Cdc42 and Rac1 in the post-Golgi transport of E-cadherin. Dominant-negative mutants of Cdc42 and Rac1 accumulate E-cadherin at a distinct post-Golgi step. This accumulation occurs before p120(ctn) interacts with E-cadherin, because p120(ctn) localization was not affected by the Cdc42 or Rac1 mutants. Moreover, the GTPase mutants had no effect on the trafficking of a targeting mutant of E-cadherin, consistent with the selective involvement of Cdc42 and Rac1 in basolateral trafficking. These results provide a new example of Rho GTPase regulation of basolateral trafficking and demonstrate novel roles for Cdc42 and Rac1 in the post-Golgi transport of E-cadherin.
Wang
Bo
B
Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Queensland, Australia.
Wylie
Fiona G
FG
Teasdale
Rohan D
RD
Stow
Jennifer L
JL
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D015870:Gene Expression; D007668:Kidney / Q000378:metabolism; D009154:Mutation; D021381:Protein Transport / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
D015820:Cadherins; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein