title: Syntaxin 3 and SNAP-25 pairing, regulated by omega-3 docosahexaenoic acid, controls the delivery of rhodopsin for the biogenesis of cilia-derived sensory organelles, the rod outer segments.
abstract: The biogenesis of cilia-derived sensory organelles, the photoreceptor rod outer segments (ROS), is mediated by rhodopsin transport carriers (RTCs). The small GTPase Rab8 regulates ciliary targeting of RTCs, but their specific fusion sites have not been characterized. Here, we report that the Sec6/8 complex, or exocyst, is a candidate effector for Rab8. We also show that the Qa-SNARE syntaxin 3 is present in the rod inner segment (RIS) plasma membrane at the base of the cilium and displays a microtubule-dependent concentration gradient, whereas the Qbc-SNARE SNAP-25 is uniformly distributed in the RIS plasma membrane and the synapse. Treatment with omega-3 docosahexaenoic acid [DHA, 22:6(n-3)] causes increased co-immunoprecipitation and colocalization of SNAP-25 and syntaxin 3 at the base of the cilium, which results in the increased delivery of membrane to the ROS. This is particularly evident in propranolol-treated retinas, in which the DHA-mediated increase in SNARE pairing overcomes the tethering block, including dissociation of Sec8 into the cytosol. Together, our data indicate that the Sec6/8 complex, syntaxin 3 and SNAP-25 regulate rhodopsin delivery, probably by mediating docking and fusion of RTCs. We show further that DHA, an essential polyunsaturated fatty acid of the ROS, increases pairing of syntaxin 3 and SNAP-25 to regulate expansion of the ciliary membrane and ROS biogenesis.
authors.affiliation: Department of Surgery, Division of Ophthalmology, University of New Mexico, Albuquerque, New Mexico 87131, USA.
authors.forename: Jana
authors.initials: J
authors.lastname: Mazelova
authors.forename: Nancy
authors.initials: N
authors.lastname: Ransom
authors.forename: Lisa
authors.initials: L
authors.lastname: Astuto-Gribble
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wilson
authors.forename: Dusanka
authors.initials: D
authors.lastname: Deretic
mesh_terms: D000818:Animals; D002923:Cilia / Q000378:metabolism / Q000502:physiology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D008954:Models, Biological; D015388:Organelles / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000378:metabolism* / Q000502:physiology; D011898:Ranidae; D012243:Rhodopsin / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism / Q000502:physiology*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism* / Q000502:physiology
chemical_list: D015525:Fatty Acids, Omega-3; D050765:Qa-SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D004281:Docosahexaenoic Acids; D012243:Rhodopsin