Nucleotide bound to rab11a controls localization in rod cells but not interaction with rhodopsin.
Precise vectorial transport of rhodopsin is essential for rod photoreceptor health and function. Mutations that truncate or extend the C terminus of rhodopsin disrupt this transport, and lead to retinal degeneration and blindness in human patients and in mouse models. Here we show that such mutations disrupt the binding of rhodopsin to the small GTPase rab11a. The rhodopsin-rab11a interaction is a direct binding interaction that does not depend on the nucleotide binding state of rab11a. Expression of EGFP-rab11a fusion proteins in Xenopus laevis photoreceptors revealed that the nucleotide binding status of rab11a affects its subcellular localization, with GTP-locked mutants concentrated in the inner segment and GDP-locked mutants concentrated in the outer segment. shRNA-mediated knockdown of rab11a in rods led to shortened outer segments and retinal degeneration. Together, our results show the critical importance of direct rhodopsin-rab11a interactions for the formation and maintenance of vertebrate photoreceptors.
Evelyn F. McKnight Brain Institute, Department of Neurobiology, and.
Nicholas J
NJ
Reish
Evelyn F. McKnight Brain Institute, Department of Vision Sciences, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama 35294.
Evan R
ER
Boitet
Evelyn F. McKnight Brain Institute, Department of Vision Sciences, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama 35294.
Katie L
KL
Bales
Evelyn F. McKnight Brain Institute, Department of Neurobiology, and Department of Vision Sciences, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama 35294 agross@uab.edu.
Alecia K
http://orcid.org/0000-0003-1857-6633
AK
Gross
D000818:Animals; D001665:Binding Sites; D006160:Guanosine Triphosphate / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D021381:Protein Transport; D012243:Rhodopsin / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism*; D014981:Xenopus; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
D006160:Guanosine Triphosphate; D012243:Rhodopsin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins
protein interactions; protein trafficking; rab11a; rhodopsin