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First published online 19 May 2009
doi: 10.1242/jcs.039982

Journal of Cell Science 122, 2003-2013 (2009)
Published by The Company of Biologists 2009
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Research Article

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

Jana Mazelova1, Nancy Ransom1, Lisa Astuto-Gribble1, Michael C. Wilson2 and Dusanka Deretic1,3,*

1 Department of Surgery, Division of Ophthalmology, University of New Mexico, Albuquerque, New Mexico 87131
2 Department of Neuroscience, University of New Mexico, Albuquerque, New Mexico 87131
3 Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico 87131

* Author for correspondence (e-mail: dderetic{at}salud.unm.edu)

Accepted 2 March 2009

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.

Key words: Rhodopsin, SNARE, Fatty acid, Cilium


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