April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
A Microtubule-Associated Protein Links to the Usher Protein Network
F. F. Kersten; E. van Wijk; L. Hetterschijt; K. Bauss; U. Wolfrum; J. E. E. Keunen; R. Roepman; H. Kremer
Author Affiliations & Notes
  • F. F. Kersten
    Human Genetics, Otorhinolaryngology, Head and Neck Surgery, Ophthalmology, Nijmegen Centre for Molecular Life Sciences; Donders Institute for brain, cognition and behaviour,
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Radboud University Nijmegen, Nijmegen, The Netherlands
  • E. van Wijk
    Human Genetics, Otorhinolaryngology, Head and Neck Surgery, Ophthalmology, Nijmegen Centre for Molecular Life Sciences; Donders Institute for brain, cognition and behaviour,
    Human Genetics, Otorhinolaryngology, Head and Neck Surgery, Nijmegen Centre for Molecular Life Sciences,
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Radboud University Nijmegen, Nijmegen, The Netherlands
  • L. Hetterschijt
    Human Genetics,
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  • K. Bauss
    Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University of Mainz, Mainz, Germany
  • U. Wolfrum
    Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University of Mainz, Mainz, Germany
  • J. E. E. Keunen
    Ophthalmology,
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  • R. Roepman
    Human Genetics, Otorhinolaryngology, Head and Neck Surgery, Nijmegen Centre for Molecular Life Sciences,
    Human Genetics,
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Radboud University Nijmegen, Nijmegen, The Netherlands
  • H. Kremer
    Human Genetics, Otorhinolaryngology, Head and Neck Surgery, Ophthalmology, Nijmegen Centre for Molecular Life Sciences; Donders Institute for brain, cognition and behaviour,
    Otorhinolaryngology, Head and Neck Surgery,
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Radboud University Nijmegen, Nijmegen, The Netherlands
  • Footnotes
    Commercial Relationships  F.F. Kersten, None; E. van Wijk, None; L. Hetterschijt, None; K. Bauss, None; U. Wolfrum, None; J.E.E. Keunen, None; R. Roepman, None; H. Kremer, None.
  • Footnotes
    Support  Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands and The British Retinitis Pigmentosa Society (GR552)
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2595. doi:
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      F. F. Kersten, E. van Wijk, L. Hetterschijt, K. Bauss, U. Wolfrum, J. E. E. Keunen, R. Roepman, H. Kremer; A Microtubule-Associated Protein Links to the Usher Protein Network. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2595.

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Abstract

Purpose: : Usher syndrome is the most common form of combined hereditary deaf-blindness in man. It is caused by mutations in genes encoding proteins with a variety of functions, but that all closely associate in a protein network. Nevertheless, the molecular disease mechanisms of Usher syndrome still remain largely elusive. To gain insight into the pathogenic pathways underlying Usher type 2A (USH2A), we have set out to determine the interacting repertoire of the USH2A isoform B protein in the retina.

Methods: : Interactors were identified in a yeast two-hybrid (Y2H) screen of a human retinal cDNA library, using the intracellular domain of USH2A as a bait. Putative interactions were validated by glutathione S-transferase (GST) pull-down assays and by (co-) localization studies in the rat retina, employing immunofluorescence and immunoelectron microscopy.

Results: : The Y2H screen revealed several interesting interactors, including a microtubule-associated protein of 134 kDa (indicated as MAP134). The intracellular domain of USH2A specifically interacts with the two coiled coil domains of this protein. The interaction was confirmed by GST pull-down assays and these proteins co-localize at several sub-cellular sites in photoreceptor cells, including the basal body. Immunoelectron microscopy showed presence of both USH2A and MAP134 in the apical inner segment, connecting cilium, basal body and centriole of photoreceptor cells.

Conclusions: : Our data indicate that USH2A specifically interacts with MAP134 and that the two proteins co-localize in the photoreceptor cells. We thus introduce a novel member of the Usher protein network that is known to play a role in microtubule stabilization. This permits the hypothesis that MAP134 is involved in the structural maintenance of the connecting cilium and/or in the microtubule-based transport in the photoreceptor cells. Its direct association with USH2A indicates that the gene encoding MAP134 is a functional candidate for Usher syndrome or related retinal ciliopathies.

Keywords: proteins encoded by disease genes • ciliary processes 
© 2010, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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