Cellular retinol binding protein 1 modulates photoreceptor outer segment folding in the isolated eye.
In a previous study, we used differential proteomics to identify retinal proteins whose steady-state levels were altered in an experimental system in which photoreceptor outer segments were improperly folded. We determined that the steady-state level of cellular retinol binding protein 1 (CRBP1) was downregulated in eyes lacking organized outer segments. The purpose of this study was to determine if CRBP1 is a plausible candidate for regulating outer segment assembly. We used Morpholinos to directly test the hypothesis that a decreased level of CRBP1 protein was associated with the misfolding of outer segments. Results from these studies indicate that downregulation of CRBP1 protein resulted in aberrant assembly of outer segments. Because CRBP1 plays a dual role in the retina-retinal recycling and generation of retinoic acid-we evaluated both possibilities. Our data demonstrate that outer segment folding was not modified by 11-cis retinal supplementation, suggesting that CRBP1 influences outer segment assembly through a mechanism unrelated to rhodopsin regeneration. In contrast, retinoic acid is required for the proper organization of nascent outer segment membranes. The localization of CRBP1 within Muller cells and the RPE and its demonstrated role in modulating the proper folding of nascent outer segment membranes through retinoic acid further elucidates the role of these cells in directly influencing photoreceptor physiology.
Wang
Xiaofei
X
Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Tong
Yiai
Y
Giorgianni
Francesco
F
Beranova-Giorgianni
Sarka
S
Penn
John S
JS
Jablonski
Monica M
MM
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007814:Larva; D016376:Oligonucleotides, Antisense; D012160:Retina / Q000254:growth & development* / Q000378:metabolism*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000254:growth & development / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D002352:Carrier Proteins; D016376:Oligonucleotides, Antisense; D012177:Retinol-Binding Proteins; D029867:Xenopus Proteins; C000617331:ribosome-binding protein 1, Xenopus; D014801:Vitamin A; D014212:Tretinoin