Trafficking of membrane proteins to cone but not rod outer segments is dependent on heterotrimeric kinesin-II.
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.
Avasthi
Prachee
P
Department of Ophthalmology, University of Utah Health Science Center, Salt Lake City, Utah 84132, USA.
Watt
Carl B
CB
Williams
David S
DS
Le
Yun Z
YZ
Li
Sha
S
Chen
Ching-Kang
CK
Marc
Robert E
RE
Frederick
Jeanne M
JM
Baehr
Wolfgang
W
D000818:Animals; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D012160:Retina / Q000254:growth & development / Q000503:physiopathology / Q000648:ultrastructure; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology* / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000503:physiopathology; D012168:Retinal Pigments / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D012243:Rhodopsin / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D013997:Time Factors
C490202:Kif3a protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D012168:Retinal Pigments; D012243:Rhodopsin; D016547:Kinesins