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The Journal of Neuroscience, November 11, 2009, 29(45):14287-14298; doi:10.1523/JNEUROSCI.3976-09.2009

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Neurobiology of Disease
Trafficking of Membrane Proteins to Cone But Not Rod Outer Segments Is Dependent on Heterotrimeric Kinesin-II

Prachee Avasthi,1,3 Carl B. Watt,1 David S. Williams,5 Yun Z. Le,6 Sha Li,1 Ching-Kang Chen,7 Robert E. Marc,1 Jeanne M. Frederick,1 and Wolfgang Baehr1,2,4

1Departments of Ophthalmology and 2Neurobiology and Anatomy, and 3Graduate Program in Neuroscience, University of Utah Health Science Center, Salt Lake City, Utah 84132, 4Department of Biology, University of Utah, Salt Lake City, Utah 84112, 5Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, California 90095-7065, 6Departments of Medicine and Cell Biology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, and 7Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298

Correspondence should be addressed to Wolfgang Baehr, John A. Moran Eye Center, University of Utah Health Science Center, Salt Lake City, UT 84132. Email: wbaehr{at}hsc.utah.edu

Heterotrimeric kinesin-II is a molecular motor localized to the inner segment, connecting cilium and axoneme of mammalian photoreceptors. Our purpose was to identify the role of kinesin-II in anterograde intraflagellar transport by photoreceptor-specific deletions of kinesin family member 3A (KIF3A), its obligatory motor subunit. In cones lacking KIF3A, membrane proteins involved in phototransduction did not traffic to the outer segments resulting in complete absence of a photopic electroretinogram and progressive cone degeneration. Rod photoreceptors lacking KIF3A degenerated rapidly between 2 and 4 weeks postnatally, but the phototransduction components including rhodopsin trafficked to the outer segments during the course of degeneration. Furthermore, KIF3A deletion did not affect synaptic anterograde trafficking. The results indicate that trafficking of membrane proteins to the outer segment is dependent on kinesin-II in cone, but not rod photoreceptors, even though rods and cones share similar structures, and closely related phototransduction polypeptides.

Received Aug. 13, 2009; accepted Sept. 14, 2009.

Correspondence should be addressed to Wolfgang Baehr, John A. Moran Eye Center, University of Utah Health Science Center, Salt Lake City, UT 84132. Email: wbaehr{at}hsc.utah.edu
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