Article

Rab8 Regulates Basolateral Secretory, But Not Recycling, Traffic at the Recycling Endosome

Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Molecular biology of the cell (Impact Factor: 4.47). 06/2008; 19(5):2059-68. DOI: 10.1091/mbc.E07-09-0902
Source: PubMed

ABSTRACT

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 mu1-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.

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    • "Rab GTPases regulate budding, transport, tethering and fusion of vesicles, thereby providing specificity to membrane trafficking. Rab8-mediated traffic to the PM has been classically related to the secretory exocytic pathway (Henry and Sheff, 2008; Huber et al., 1993; Peränen et al., 1996), although it is also involved in the slow recycling route (Ang et al., 2003; Hattula et al., 2006; Roland et al., 2007; Yamamura et al., 2008). Rab8 is known to regulate polarized vesicle transport to the PM and to promote actin and microtubule cytoskeletal rearrangements to mediate protrusion formation (Hattula et al., 2002; Huber et al., 1993; Peränen et al., 1996). "
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