title: The RCP-Rab11 complex regulates endocytic protein sorting.
abstract: Rab 11 GTPase is an important regulator of endocytic membrane traffic. Recently, we and others have identified a novel family of Rab11 binding proteins, known as Rab11-family interacting proteins (FIPs). One of the family members, Rab coupling protein (RCP), was identified as a protein binding to both Rab4 and Rab11 GTPases. RCP was therefore suggested to serve a dual function as Rab4 and Rab11 binding protein. In this study, we characterized the cellular functions of RCP and mapped its interactions with Rab4 and Rab11. Our data show that RCP interacts only weakly with Rab4 in vitro and does not play the role of coupling Rab11 and Rab4 in vivo. Furthermore, our data indicate that the RCP-Rab11 complex regulates the sorting of transferrin receptors from the degradative to the recycling pathway. We therefore propose that RCP functions primarily as a Rab11 binding protein that regulates protein sorting in tubular endosomes.
authors.affiliation: Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Peden
authors.forename: Eric
authors.initials: E
authors.lastname: Schonteich
authors.forename: John
authors.initials: J
authors.lastname: Chun
authors.forename: Jagath R
authors.initials: JR
authors.lastname: Junutula
authors.forename: Richard H
authors.initials: RH
authors.lastname: Scheller
authors.forename: Rytis
authors.initials: R
authors.lastname: Prekeris
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011992:Endosomes / Q000276:immunology / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C488966:RAB11FIP1 protein, human