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Deciphering the roles of prominins in the visual system

  • Denis Corbeil
    Correspondence
    To whom correspondence may be addressed: Biotechnology Center, Technische Universität Dresden, Tatzberg 47–49, 01307 Dresden, Germany. Tel.:49-351-463-40118; Fax:49-351-463-40244
    Affiliations
    Tissue Engineering Laboratories, Biotechnology Center (BIOTEC) and Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47–49, 01307 Dresden, Germany
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  • Christine A. Fargeas
    Affiliations
    Tissue Engineering Laboratories, Biotechnology Center (BIOTEC) and Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47–49, 01307 Dresden, Germany
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  • József Jászai
    Correspondence
    To whom correspondence may be addressed: Institute of Anatomy, Medizinische Fakultät der Technischen Universität Dresden, Fiedlerstr. 42, 01307 Dresden, Germany. Tel.:49-351-458-6085; Fax:49-351-458-6303
    Affiliations
    Institute of Anatomy, Medizinische Fakultät der Technischen Universität Dresden, Fiedlerstrasse 42, 01307 Dresden, Germany
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Open AccessPublished:November 08, 2019DOI:https://doi.org/10.1074/jbc.L119.011198
      The mammalian Prom1 gene, which is critical for photoreceptor membrane biogenesis through its interaction with protocadherin 21 (
      • Yang Z.
      • Chen Y.
      • Lillo C.
      • Chien J.
      • Yu Z.
      • Michaelides M.
      • Klein M.
      • Howes K.A.
      • Li Y.
      • Kaminoh Y.
      • Chen H.
      • Zhao C.
      • Chen Y.
      • Al-Sheikh Y.T.
      • Karan G.
      • et al.
      Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice.
      ), has two zebrafish orthologs (prom1a and prom1b). In situ hybridization revealed co-expression of their transcripts in neural tissues and in the outer nuclear layer of the retina where perikarya of photoreceptors reside (
      • Jászai J.
      • Fargeas C.A.
      • Graupner S.
      • Tanaka E.M.
      • Brand M.
      • Huttner W.B.
      • Corbeil D.
      Distinct and conserved prominin-1/CD133-positive retinal cell populations identified across species.
      ,
      • Jászai J.
      • Graupner S.
      • Tanaka E.M.
      • Funk R.H.
      • Huttner W.B.
      • Brand M.
      • Corbeil D.
      Spatial distribution of prominin-1 (CD133)-positive cells within germinative zones of the vertebrate brain.
      ). In contrast to mice, both orthologs were strongly and differentially expressed by retinal interneurons in the inner nuclear layer of the adult fish retina (
      • Jászai J.
      • Fargeas C.A.
      • Graupner S.
      • Tanaka E.M.
      • Brand M.
      • Huttner W.B.
      • Corbeil D.
      Distinct and conserved prominin-1/CD133-positive retinal cell populations identified across species.
      ). Therein, prom1a transcripts were confined to the vitreal side, whereas prom1b was detected on the scleral side of the layer harboring bipolar and horizontal cells. We were consequently intrigued by the data of Lu et al. (
      • Lu Z.
      • Hu X.
      • Reilly J.
      • Jia D.
      • Liu F.
      • Yu S.
      • Liu X.
      • Xie S.
      • Qu Z.
      • Qin Y.
      • Huang Y.
      • Lv Y.
      • Li J.
      • Gao P.
      • Wong F.
      • et al.
      Deletion of the transmembrane protein Prom1b in zebrafish disrupts outer-segment morphogenesis and causes photoreceptor degeneration.
      ) indicating that the deletion of Prom1b only disrupted outer-segment morphogenesis and that Prom1a had little part in this process.
      Actually, both proteins are strongly expressed in the retina, as was shown by immunoblotting (
      • Jászai J.
      • Fargeas C.A.
      • Graupner S.
      • Tanaka E.M.
      • Brand M.
      • Huttner W.B.
      • Corbeil D.
      Distinct and conserved prominin-1/CD133-positive retinal cell populations identified across species.
      ), and native prom1a is properly N-glycosylated (
      • Jászai J.
      • Fargeas C.A.
      • Graupner S.
      • Tanaka E.M.
      • Brand M.
      • Huttner W.B.
      • Corbeil D.
      Distinct and conserved prominin-1/CD133-positive retinal cell populations identified across species.
      ). Therefore, data obtained with ectopic expression of recombinant prom1a should be interpreted with caution. At least five splice variants of zebrafish prom1a have been identified, and more than one is expressed in zebrafish retina (
      • Jászai J.
      • Fargeas C.A.
      • Graupner S.
      • Tanaka E.M.
      • Brand M.
      • Huttner W.B.
      • Corbeil D.
      Distinct and conserved prominin-1/CD133-positive retinal cell populations identified across species.
      ). Moreover, some of them may not reach the cell surface, as reported for certain murine prom1 variants (
      • Fargeas C.A.
      • Joester A.
      • Missol-Kolka E.
      • Hellwig A.
      • Huttner W.B.
      • Corbeil D.
      Identification of novel Prominin-1/CD133 splice variants with alternative C-termini and their expression in epididymis and testis.
      ). Unfortunately, no information is available about the prom1a/b sequences (and potential splicing variants) presented by Lu et al. (
      • Lu Z.
      • Hu X.
      • Reilly J.
      • Jia D.
      • Liu F.
      • Yu S.
      • Liu X.
      • Xie S.
      • Qu Z.
      • Qin Y.
      • Huang Y.
      • Lv Y.
      • Li J.
      • Gao P.
      • Wong F.
      • et al.
      Deletion of the transmembrane protein Prom1b in zebrafish disrupts outer-segment morphogenesis and causes photoreceptor degeneration.
      ). To provide new perspectives in this field, subcellular confinement of prom1b in photoreceptors, its potential interaction with protocadherin, and, more importantly, the functional relevance of prom1b deficiency on the visual system should have been shown.

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