MPP3 regulates levels of PALS1 and adhesion between photoreceptors and Müller cells

Jacobus J Dudok, Alicia Sanz Sanz, Ditte M S Lundvig, Vithiyanjali Sothilingam, Marina Garcia Garrido, Jan Klooster, Mathias W Seeliger, Jan Wijnholds

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Abstract

MPP3 and CRB1 both interact directly with PALS1/MPP5 and through this scaffold protein may form a large protein complex. To investigate the role of MPP3 in the retina we have analyzed conditional mutant Mpp3 knockout mice. Ultrastructural localization studies revealed that MPP3 is predominantly localized in apical villi of Müller glia cells. Retinas lacking MPP3 developed late onset retinal degeneration, with sporadic foci of rosette formation in the central part of the retina. Retinal degeneration in Mpp3 cKO mice was accelerated by exposure to moderate levels of white light. Electroretinography recordings in aging mice under both scotopic and photopic conditions ranged from normal to mildly subnormal, while the magnitude correlated with the strength and extent of morphological alterations. Loss of MPP3 resulted in significant loss of PALS1 at the subapical region adjacent to adherens junctions, and loss of MPP3 in Pals1 conditional knockdown retinas significantly accelerated the onset of retinal degeneration. These data suggest that MPP3 is required for maintaining proper levels of PALS1 at the subapical region, and indicate that the MPP3 gene is a candidate modulator of the Crumbs complex.

Original languageEnglish
Pages (from-to)1629-1644
Number of pages16
JournalGlia
Volume61
Issue number10
DOIs
Publication statusPublished - Oct 2013

Keywords

  • Animals
  • Catenins
  • Cell Adhesion
  • Cell Adhesion Molecules
  • Electroretinography
  • Ependymoglial Cells
  • Fluorescein Angiography
  • Gene Expression Regulation
  • Guanylate Kinases
  • Light
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Immunoelectron
  • Nucleoside-Phosphate Kinase
  • Photoreceptor Cells
  • Retina
  • Retinal Degeneration
  • Tomography, Optical Coherence
  • Visual Pathways
  • Journal Article
  • Research Support, Non-U.S. Gov't

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    Dudok, J. J., Sanz, A. S., Lundvig, D. M. S., Sothilingam, V., Garcia Garrido, M., Klooster, J., ... Wijnholds, J. (2013). MPP3 regulates levels of PALS1 and adhesion between photoreceptors and Müller cells. Glia, 61(10), 1629-1644. https://doi.org/10.1002/glia.22545