Direct interaction between Rab3b and the polymeric immunoglobulin receptor controls ligand-stimulated transcytosis in epithelial cells.
We have examined the role of rab3b in epithelial cells. In MDCK cells, rab3b localizes to vesicular structures containing the polymeric immunoglobulin receptor (pIgR) and located subjacent to the apical surface. We found that GTP-bound rab3b directly interacts with the cytoplasmic domain of pIgR. Binding of dIgA to pIgR causes a dissociation of the interaction with rab3b, a process that requires dIgA-mediated signaling, Arg657 in the cytoplasmic domain of pIgR, and possibly GTP hydrolysis by rab3b. Binding of dIgA to pIgR at the basolateral surface stimulates subsequent transcytosis to the apical surface. Overexpression of GTP-locked rab3b inhibits dIgA-stimulated transcytosis. Together, our data demonstrate that a rab protein can bind directly to a specific cargo protein and thereby control its trafficking.
van IJzendoorn
Sven C D
SC
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Tuvim
Michael J
MJ
Weimbs
Thomas
T
Dickey
Burton F
BF
Mostov
Keith E
KE
D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D019281:Dimerization; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D007070:Immunoglobulin A / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D019056:Receptors, Polymeric Immunoglobulin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D007070:Immunoglobulin A; D008024:Ligands; D019056:Receptors, Polymeric Immunoglobulin; D006160:Guanosine Triphosphate; D020692:rab3 GTP-Binding Proteins