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: We next sought to determine whether TBC1D9B had GAP activity against any of its binding partners. We first performed comparative protein structure modeling using the known three-dimensional (3D) structure of the TBC1D4 TBC domain as a template (Protein Data Bank [PDB] file 3QYB; Park et al., 2011). Figure 3A shows the predicted structure of the TBC domain of TBC1D9B superimposed on the known structure of the TBC1D4 TBC domain. The structural overlap parameter obtained was 64%, confirming that the two structures were structurally related (Geourjon et al., 2001). In addition, the putative catalytic residues (R559, Y592, and Q594) of TBC1D9B were exposed similarly to those of TBC1D4 and other TBC proteins such as Gyp1p (unpublished data). Thus, the sequence homologies and predicted structure are consistent with the possibility that TBC1D9B was a functional GAP.
Affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.