title: MPP3 regulates levels of PALS1 and adhesion between photoreceptors and Müller cells.
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.
authors.affiliation: Department of Neuromedical Genetics, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105, BA Amsterdam, The Netherlands.
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: Dudok
authors.forename: Alicia Sanz
authors.initials: AS
authors.lastname: Sanz
authors.forename: Ditte M S
authors.initials: DM
authors.lastname: Lundvig
authors.forename: Vithiyanjali
authors.initials: V
authors.lastname: Sothilingam
authors.forename: Marina
authors.initials: M
authors.lastname: Garcia Garrido
authors.forename: Jan
authors.initials: J
authors.lastname: Klooster
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
authors.forename: Jan
authors.initials: J
authors.lastname: Wijnholds
mesh_terms: D000818:Animals; D051177:Catenins / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004596:Electroretinography; D063928:Ependymoglial Cells / Q000378:metabolism* / Q000648:ultrastructure; D005451:Fluorescein Angiography; D005786:Gene Expression Regulation / Q000235:genetics; D051528:Guanylate Kinases / Q000172:deficiency / Q000378:metabolism*; D008027:Light / Q000009:adverse effects; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D000075983:Nectins; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000378:metabolism* / Q000648:ultrastructure; D012160:Retina / Q000166:cytology; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology; D041623:Tomography, Optical Coherence; D014795:Visual Pathways / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D015815:Cell Adhesion Molecules; C568885:Crb2 protein, mouse; D008565:Membrane Proteins; D000075983:Nectins; D009703:Nucleoside-Phosphate Kinase; C491075:Dlgh3 protein, mouse; D051528:Guanylate Kinases; C499979:Mpp5 protein, mouse; D000095002:Delta Catenin
keywords: Crumbs complex; Müller glia; adherens junctions; aging; retinal degeneration