title: MPP3 is recruited to the MPP5 protein scaffold at the retinal outer limiting membrane.
abstract: Mutations in the human Crumbs homologue 1 (CRB1) gene are a frequent cause of various forms of retinitis pigmentosa. The CRB1-membrane-associated palmitoylated protein (MPP)5 protein complex is thought to organize an intracellular protein scaffold in the retina that is involved in maintenance of photoreceptor-Müller glia cell adhesion. This study focused on the binding characteristics and subcellular localization of MPP3, a novel member of the MPP5 protein scaffold at the outer limiting membrane (OLM), and of the DLG1 protein scaffold at the outer plexiform layer of the retina. MPP3 localized at the photoreceptor synapse and at the subapical region adjacent to adherens junctions at the OLM. Localization studies in human retinae revealed that MPP3 colocalized with MPP5 and CRB1 at the subapical region. MPP3 and MPP4 colocalized with DLG1 at the outer plexiform layer. Mouse Dlg1 formed separate complexes with Mpp3 and Mpp4 in vivo. These data implicate a role for MPP3 in photoreceptor polarity and, by association with MPP5, pinpoint MPP3 as a functional candidate gene for inherited retinopathies. The separate Mpp3/Dlg1 and Mpp4/Dlg1 complexes at the outer plexiform layer point towards additional yet unrecognized functions of these membrane associated guanylate kinase proteins.
authors.affiliation: Department of Neuromedical Genetics, The Netherlands Institute for Neurosciences (NIN), KNAW, Amsterdam, The Netherlands.
authors.forename: Albena
authors.initials: A
authors.lastname: Kantardzhieva
authors.forename: Svetlana
authors.initials: S
authors.lastname: Alexeeva
authors.forename: Inge
authors.initials: I
authors.lastname: Versteeg
authors.forename: Jan
authors.initials: J
authors.lastname: Wijnholds
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000074288:Discs Large Homolog 1 Protein; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D051528:Guanylate Kinases / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D011487:Protein Conformation; D020033:Protein Isoforms / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C448939:CRB1 protein, human; C513314:DLG1 protein, human; C116869:DLG3 protein, human; D000074288:Discs Large Homolog 1 Protein; C000614189:Dlg1 protein, mouse; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C470950:MPP4 protein, human; C501307:MPP5 protein, human