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Vol. 19, Issue 5, 2059-2068, May 2008
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Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Submitted September 17, 2007;
Revised February 5, 2008;
Accepted February 11, 2008
Monitoring Editor: Jennifer Lippincott-Schwartz
Rab8 is a monomeric GTPase that regulates the delivery of newly synthesized proteins to the basolateral surface in polarized epithelial cells. Recent publications have demonstrated that basolateral proteins interacting with the µ1-B clathrin adapter subunit pass through the recycling endosome (RE) en route from the TGN to the plasma membrane. Because Rab8 interacts with these basolateral proteins, these findings raise the question of whether Rab8 acts before, at, or after the RE. We find that Rab8 overexpression during the formation of polarity in MDCK cells, disrupts polarization of the cell, explaining how Rab8 mutants can disrupt basolateral endocytic and secretory traffic. However, once cells are polarized, Rab8 mutants cause mis-sorting of newly synthesized basolateral proteins such as VSV-G to the apical surface, but do not cause mis-sorting of membrane proteins already at the cell surface or in the endocytic recycling pathway. Enzymatic ablation of the RE also prevents traffic from the TGN from reaching the RE and similarly results in mis-sorting of newly synthesized VSV-G. We conclude that Rab8 regulates biosynthetic traffic through REs to the plasma membrane, but not trafficking of endocytic cargo through the RE. The data are consistent with a model in which Rab8 functions in regulating the delivery of TGN-derived cargo to REs.
Address correspondence to: David R. Sheff (david-sheff{at}uiowa.edu)
Abbreviations used: CHO, Chinese Hamster ovary; MDCK, Madin-Darby canine kidney; MDCKT, MDCK cell with transferrin receptor; RE, recycling endosome; RFP, red fluorescent protein; TER, trans epithelial resistance; TGN, trans-Golgi network; Tfn, transferrin.
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