title: The centrosome regulates the Rab11- dependent recycling endosome pathway at appendages of the mother centriole.
abstract: The recycling endosome localizes to a pericentrosomal region via microtubule-dependent transport. We previously showed that Sec15, an effector of the recycling endosome component, Rab11-GTPase, interacts with the mother centriole appendage protein, centriolin, suggesting an interaction between endosomes and centrosomes. Here we show that the recycling endosome associates with the appendages of the mother (older) centriole. We show that two mother centriole appendage proteins, centriolin and cenexin/ODF2, regulate association of the endosome components Rab11, the Rab11 GTP-activating protein Evi5, and the exocyst at the mother centriole. Development of an in vitro method for reconstituting endosome protein complexes onto isolated membrane-free centrosomes demonstrates that purified GTP-Rab11 but not GDP-Rab11 binds to mother centriole appendages in the absence of membranes. Moreover, centriolin depletion displaces the centrosomal Rab11 GAP, Evi5, and increases mother-centriole-associated Rab11; depletion of Evi5 also increases centrosomal Rab11. This indicates that centriolin localizes Evi5 to centriolar appendages to turn off centrosomal Rab11 activity. Finally, centriolin depletion disrupts recycling endosome organization and function, suggesting a role for mother centriole proteins in the regulation of Rab11 localization and activity at the mother centriole.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Biotech 2, Suite 206, 373 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hehnly
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Chen
authors.forename: Christine M
authors.initials: CM
authors.lastname: Powers
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Liu
authors.forename: Stephen
authors.initials: S
authors.lastname: Doxsey
mesh_terms: D001692:Biological Transport; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002502:Centrioles / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics; D020690:GTPase-Activating Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D018797:Cell Cycle Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020690:GTPase-Activating Proteins; D006160:Guanosine Triphosphate; D006360:Heat-Shock Proteins; D034904:Lamin Type A; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C474898:CNTRL protein, human; C506399:EVI5 protein, human; C490685:EXOC3 protein, human; C489222:EXOC6B protein, human; C494847:LMNA protein, human; C490107:ODF2 protein, human