Zebrafish Crb1, localizing uniquely to the cell membranes around cone photoreceptor axonemes, alleviates light damage to photoreceptors and modulates cones' light responsiveness

Guo, C., Deveau, C., Zhang, C., Nelson, R., Wei, X.
The Journal of neuroscience : the official journal of the Society for Neuroscience   40(37): 7065-7079 (Journal)
Registered Authors
Nelson, Ralph, Wei, Xiangyun
MeSH Terms
  • Animals
  • Axoneme/metabolism*
  • Cell Membrane/metabolism
  • Cell Membrane/physiology
  • Chromatin/metabolism
  • Female
  • Male
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Protein Transport
  • Retinal Cone Photoreceptor Cells/metabolism*
  • Retinal Cone Photoreceptor Cells/physiology
  • Retinal Cone Photoreceptor Cells/radiation effects
  • Ultraviolet Rays/adverse effects
  • Vision, Ocular*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
32817065 Full text @ J. Neurosci.
The crumbs (crb) apical polarity genes are essential for the development and functions of epithelia. Adult zebrafish retinal neuroepithelium expresses three crb genes (crb1, crb2a, and crb2b); however, it is unknown whether and how Crb1 differs from other Crb proteins in expression, localization, and functions. Here, we show that, unlike zebrafish Crb2a and Crb2b as well as mammalian Crb1 and Crb2, zebrafish Crb1 does not localize to the subapical regions (SARs) of photoreceptors and Müller glial cells; rather, it localizes to a small region of cone outer segments-the cell membranes surrounding the axonemes. Moreover, zebrafish Crb1 is not required for retinal morphogenesis and photoreceptor patterning. Interestingly, Crb1 promotes rod survival under strong white light irradiation in a previously unreported non-cell-autonomous fashion; in addition, Crb1 delays UV and blue cones' chromatin condensation caused by UV light irradiation. Finally, Crb1 plays a role in cones' responsiveness to light through an arrestin-translocation-independent mechanism. The localization of Crb1 and its functions do not differ between male and female fish. We conclude that zebrafish Crb1 has diverged from other vertebrate Crb proteins, representing a neofunctionalization in Crb biology during evolution.Significance StatementApicobasal polarity of epithelia is an important property that underlies the morphogenesis and functions of epithelial tissues. Epithelial apicobasal polarity is controlled by many polarity genes, including the crb genes. In vertebrates, multiple crb genes have been identified, but the differences in their expression patterns and functions are not fully understood. Here, we report a novel subcellular localization of zebrafish Crb1 in retinal cone photoreceptors and evidence for its new functions in photoreceptor maintenance and light responsiveness. This study expands our understanding of the biology of the crb genes in epithelia, including retinal neuroepithelium.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes