PUBLICATION
Dawn and dusk peaks of outer segment phagocytosis, and visual cycle function require Rab28
- Authors
- Moran, A.L., Carter, S.P., Kaylor, J.J., Jiang, Z., Broekman, S., Dillon, E.T., Gómez Sánchez, A., Minhas, S.K., van Wijk, E., Radu, R.A., Travis, G.H., Carey, M., Blacque, O.E., Kennedy, B.N.
- ID
- ZDB-PUB-220427-9
- Date
- 2022
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36: e22309 (Journal)
- Registered Authors
- Kennedy, Breandan N., van Wijk, Erwin
- Keywords
- Rab28, bisretinoids, cilia, ciliopathy, cone-rod dystrophy, outer segment, phagocytosis, retinoids, visual cycle, zebrafish
- MeSH Terms
-
- Animals
- Blindness/metabolism
- Humans
- Phagocytosis
- Proteomics*
- Retinal Cone Photoreceptor Cells/metabolism
- Retinoids/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- rab GTP-Binding Proteins/genetics
- rab GTP-Binding Proteins/metabolism
- PubMed
- 35471581 Full text @ FASEB J.
Citation
Moran, A.L., Carter, S.P., Kaylor, J.J., Jiang, Z., Broekman, S., Dillon, E.T., Gómez Sánchez, A., Minhas, S.K., van Wijk, E., Radu, R.A., Travis, G.H., Carey, M., Blacque, O.E., Kennedy, B.N. (2022) Dawn and dusk peaks of outer segment phagocytosis, and visual cycle function require Rab28. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 36:e22309.
Abstract
RAB28 is a farnesylated, ciliary G-protein. Patient variants in RAB28 are causative of autosomal recessive cone-rod dystrophy (CRD), an inherited human blindness. In rodent and zebrafish models, the absence of Rab28 results in diminished dawn, photoreceptor, outer segment phagocytosis (OSP). Here, we demonstrate that Rab28 is also required for dusk peaks of OSP, but not for basal OSP levels. This study further elucidated the molecular mechanisms by which Rab28 controls OSP and inherited blindness. Proteomic profiling identified factors whose expression in the eye or whose expression at dawn and dusk peaks of OSP is dysregulated by loss of Rab28. Notably, transgenic overexpression of Rab28, solely in zebrafish cones, rescues the OSP defect in rab28 KO fish, suggesting rab28 gene replacement in cone photoreceptors is sufficient to regulate Rab28-OSP. Rab28 loss also perturbs function of the visual cycle as retinoid levels of 11-cRAL, 11cRP, and atRP are significantly reduced in larval and adult rab28 KO retinae (p < .05). These data give further understanding on the molecular mechanisms of RAB28-associated CRD, highlighting roles of Rab28 in both peaks of OSP, in vitamin A metabolism and in retinoid recycling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping