May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Elipsa - A Key Determinant of Photoreceptor Outer Segment Differentiation
Author Affiliations & Notes
  • J. Malicki
    Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Y. Omori
    Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  J. Malicki, None; Y. Omori, None.
  • Footnotes
    Support  EY016859; EY14104
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4034. doi:https://doi.org/
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    • Get Citation

      J. Malicki, Y. Omori; Elipsa - A Key Determinant of Photoreceptor Outer Segment Differentiation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4034. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To determine the genetic basis of vertebrate photoreceptor differentiation

Methods: : We relay on genetic approaches in the zebrafish model to identify loci involved in photoreceptor formation and survival.

Results: : Mutations in the zebrafish elipsa locus prevent the differentiation of photoreceptor outer segments and result in rapid photoreceptor degeneration. In addition to photoreceptor loss, mutant animals display early ciliogenesis defects in auditory hair cells, olfactory sensory neurons, the spinal canal, and the pronephros. These phenotypes resemble several human syndromic forms of blindness, including Bardet-Biedl Syndrome (BBS). Using the positional candidate approach, we found that the elipsa gene encodes a coiled-coil protein enriched in basal bodies and ciliary axoneme of sensory neurons as well as other tissues that feature prominent cilia. In search for Elipsa-binding partners, we performed a yeast two-hybrid screen and identified several proteins, including IFT20 and a Rab-GTPase effector. In agreement with yeast two-hybrid data, morpholino knockdown indicates that the Ift20 gene is required for the ciliary localization of Elipsa. The second putative Elipsa-binding partner, a Rab effector, appears to localize to the cytoplasm surrounding the basal body, and its knockdown in the elipsa-deficient background results in a shortening of cilia. Using genetic and biochemical approaches we show Elipsa-associated Rab effector interacts with Rab8, a small-GTPase previously shown to localize to the ciliary membrane.

Conclusions: : Elipsa and its interacting partners bridge the IFT particle and the ciliary membrane. Defects in this mechanism may result in human blindness

Keywords: photoreceptors • genetics • degenerations/dystrophies 
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