title: Small GTPases Rab8a and Rab11a Are Dispensable for Rhodopsin Transport in Mouse Photoreceptors.
abstract: Rab11a and Rab8a are ubiquitous small GTPases shown as required for rhodopsin transport in Xenopus laevis and zebrafish photoreceptors by dominant negative (dn) disruption of function. Here, we generated retina-specific Rab11a (retRab11a) and Rab8a (retRab8a) single and double knockout mice to explore the consequences in mouse photoreceptors. Rhodopsin and other outer segment (OS) membrane proteins targeted correctly to OS and electroretinogram (ERG) responses in all three mutant mouse lines were indistinguishable from wild-type (WT). Further, AAV (adeno-associated virus)-mediated expression of dnRab11b in retRab11a-/- retina, or expression of dnRab8b in retRab8a-/- retina did not cause OS protein mislocalization. Finally, a retRab8a-/- retina injected at one month of age with AAVs expressing dnRab11a, dnRab11b, dnRab8b, and dnRab10 (four dn viruses on Rab8a-/- background) and harvested three months later exhibited normal OS protein localization. In contrast to results obtained with dnRab GTPases in Xenopus and zebrafish, mouse Rab11a and Rab8a are dispensable for proper rhodopsin and outer segment membrane protein targeting. Absence of phenotype after expression of four dn Rab GTPases in a Rab8a-/- retina suggests that Rab8b and Rab11b paralogs maybe dispensable as well. Our data thus demonstrate significant interspecies variation in photoreceptor membrane protein and rhodopsin trafficking.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah Health Science Center, Salt Lake City, UT, 84132, United States of America.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Ying
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah Health Science Center, Salt Lake City, UT, 84132, United States of America.
authors.forename: Cecilia D
authors.initials: CD
authors.lastname: Gerstner
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah Health Science Center, Salt Lake City, UT, 84132, United States of America.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Frederick
authors.affiliation: Department of Ophthalmology, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610, United States of America.
authors.forename: Sanford L
authors.initials: SL
authors.lastname: Boye
authors.affiliation: Department of Ophthalmology, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610, United States of America.
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah Health Science Center, Salt Lake City, UT, 84132, United States of America.|Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT, 84132, United States of America.|Department of Biology, University of Utah, Salt Lake City, UT, 84112, United States of America.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baehr
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055786:Gene Knockout Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D010786:Photoreceptor Cells / Q000378:metabolism*; D021381:Protein Transport; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D012243:Rhodopsin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C546061:Rab8a protein, mouse