Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors.
To test whether kinesin-II is important for transport in the mammalian photoreceptor cilium, and to identify its potential cargoes, we used Cre-loxP mutagenesis to remove the kinesin-II subunit, KIF3A, specifically from photoreceptors. Complete loss of KIF3A caused large accumulations of opsin, arrestin, and membranes within the photoreceptor inner segment, while the localization of alpha-transducin was unaffected. Other membrane, organelle, and transport markers, as well as opsin processing appeared normal. Loss of KIF3A ultimately caused apoptotic photoreceptor cell death similar to a known opsin transport mutant. The data suggest that kinesin-II is required to transport opsin and arrestin from the inner to the outer segment and that blocks in this transport pathway lead to photoreceptor cell death as found in retinitis pigmentosa.
Marszalek
J R
JR
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093, USA.
Liu
X
X
Roberts
E A
EA
Chui
D
D
Marth
J D
JD
Williams
D S
DS
Goldstein
L S
LS
D000818:Animals; D017209:Apoptosis; D019393:Arrestin / Q000378:metabolism*; D001692:Biological Transport; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002923:Cilia; D005260:Female; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000502:physiology*; D008297:Male; D008322:Mammals; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000378:metabolism*; D017299:Rod Opsins / Q000378:metabolism*
D019393:Arrestin; D002135:Calcium-Binding Proteins; C087415:KIF3A protein, human; C490202:Kif3a protein, mouse; D009124:Muscle Proteins; D017299:Rod Opsins; C074152:kinesin-II; D016547:Kinesins