Nucleotide bound to rab11a controls localization in rod cells but not interaction with rhodopsin.
| Autor: | Reish NJ; Evelyn F. McKnight Brain Institute, Department of Neurobiology, and., Boitet ER; Evelyn F. McKnight Brain Institute, Department of Vision Sciences, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama 35294., Bales KL; Evelyn F. McKnight Brain Institute, Department of Vision Sciences, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama 35294., Gross AK; 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. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2014 Nov 05; Vol. 34 (45), pp. 14854-63. Date of Electronic Publication: 2014 Nov 05. |
| DOI: | 10.1523/JNEUROSCI.1943-14.2014 |
| Abstrakt: | 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. (Copyright © 2014 the authors 0270-6474/14/3414854-10$15.00/0.) |
| Databáze: | MEDLINE |
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