TBC1D9B functions as a GTPase-activating protein for Rab11a in polarized MDCK cells.
Bottom Line: In contrast, TBC1D9B had no effect on two Rab11a-independent pathways--basolateral recycling of the transferrin receptor or degradation of the epidermal growth factor receptor.Finally, expression of TBC1D9B decreased the amount of active Rab11a in the cell and concomitantly disrupted the interaction between Rab11a and its effector, Sec15A.We conclude that TBC1D9B is a Rab11a GAP that regulates basolateral-to-apical transcytosis in polarized MDCK cells.
Affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.Show MeSH
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Mentions: Next, we determined whether TBC1D9B was localized to vesicle populations where Rab11a was likely to be in its active, GTP-bound state. One such vesicle pool is the apical recycling endosome, which is accessed by the pIgR late in its transit from the basolateral-to-apical poles of the cell (Apodaca et al., 1994; Casanova et al., 1999; Wang et al., 2000a). As predicted, endogenous TBC1D9B colocalized with Rab11a and the basolaterally internalized pIgR ligand, IgA, in subapical vesicles (coefficient of colocalization of 0.59 ± 0.02; Figure 7, A and D). In addition, TBC1D9B colocalized with vesicles positive for the pIgR (coefficient of colocalization of 0.54 ± 0.07; Figure 7, B and D) or the Rab11a (and Rab8a) effector, Sec15A, one subunit of the octameric exocyst complex (coefficient of colocalization of 0.33 ± 0.04; Figure 7, C and D; Guo et al., 1999; Zhang et al., 2004; Wu et al., 2005; Novick et al., 2006; Oztan et al., 2007).
Affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.