title: The Arf and Rab11 effector FIP3 acts synergistically with ASAP1 to direct Rabin8 in ciliary receptor targeting.
abstract: Primary cilia have gained considerable importance in biology and disease now that their involvement in a wide range of human ciliopathies has been abundantly documented. However, detailed molecular mechanisms for specific targeting of sensory receptors to primary cilia are still unknown. Here, we show that the Arf and Rab11 effector FIP3 (also known as RAB11FIP3) promotes the activity of Rab11a and the Arf GTPase-activating protein (GAP) ASAP1 in the Arf4-dependent ciliary transport of the sensory receptor rhodopsin. During its passage out of the photoreceptor Golgi and trans-Golgi network (TGN), rhodopsin indirectly interacts with FIP3 through Rab11a and ASAP1. FIP3 competes with rhodopsin for binding to ASAP1 and displaces it from the ternary complex with Arf4-GTP and ASAP1. Resembling the phenotype resulting from </emph>lack of ASAP1, ablation of FIP3 abolishes ciliary targeting and causes rhodopsin mislocalization. FIP3 coordinates the interactions of ASAP1 and Rab11a with the Rab8 guanine nucleotide exchange factor Rabin8 (also known as RAB3IP). Our study implies that FIP3 functions as a crucial targeting regulator, which impinges on rhodopsin-ASAP1 interactions and shapes the binding pocket for Rabin8 within the ASAP1-Rab11a-FIP3 targeting complex, thus facilitating the orderly assembly and activation of the Rab11-Rabin8-Rab8 cascade during ciliary receptor trafficking.
authors: Department of Surgery, Division of Ophthalmology, University of New Mexico, Albuquerque, NM 87131, USA.
authors: Jing
authors: J
authors: Wang
authors: Department of Surgery, Division of Ophthalmology, University of New Mexico, Albuquerque, NM 87131, USA Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM 87131, USA dderetic@salud.unm.edu.
authors: Dusanka
authors: D
authors: Deretic
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D000081410:Germinal Center Kinases; D006801:Humans; D051379:Mice; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D020727:ADP-Ribosylation Factors; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000081410:Germinal Center Kinases; D017346:Protein Serine-Threonine Kinases; D012243:Rhodopsin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C117891:ASAP1 protein, human; C439063:RAB11FIP3 protein, human; C116688:ARF4 protein, human
keywords: Cilium; Rab11a; Rhodopsin