Membrane-associated guanylate kinase proteins MPP4 and MPP5 associate with Veli3 at distinct intercellular junctions of the neurosensory retina.
MPP4 and MPP5 are closely related members of the p55-subfamily of membrane-associated guanylate kinases (MAGUKs) known to mediate the assembly of protein complexes at the plasma membrane of cell-cell junctions. Both MPP4 and MPP5 have been implicated in retinal function; however, their specific roles in the cellular mechanisms underlying vision are largely unknown. Here, we generated specific poly- and monoclonal antibodies against the two proteins and show that MPP4 and MPP5 are localized at distinct sites of cell-cell contact in the mouse retina. While MPP4 is a component of the synaptic terminals of photoreceptors, MPP5 exclusively localizes to apical membrane domains of the outer limiting membrane (OLM) junctions. The vertebrate homologs of Caenorhabditis elegans lin-7, Veli1, -2, and -3, have previously been identified as putative binding partners of MPP5. In this study, we show that MPP4 directly interacts with the Veli proteins via L27 heterodimerization in vitro. In addition, two of the three Veli isoforms, Veli1 and -3, are demonstrated to be expressed in the mouse retina. Immunofluorescence microscopy reveals extensive colocalization of Veli3 with both MPP4 and MPP5. This association of Veli3 with either MPP4 or MPP5 suggests that the MAGUKs recruit Veli3 and its binding partners to different cellular regions of the retina where they may participate in the organization of specialized intercellular junctions.
Stöhr
Heidi
H
Institut für Humangenetik, Biozentrum, Am Hubland, Universität Würzburg, 97074 Würzburg, Germany. heidi.stoehr@biozentrum.uni-wuerzburg.de
Molday
Laurie L
LL
Molday
Robert S
RS
Weber
Bernhard H F
BH
Biedermann
Bernd
B
Reichenbach
Andreas
A
Krämer
Franziska
F
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D002417:Cattle; D051528:Guanylate Kinases; D006801:Humans; D015151:Immunoblotting; D007365:Intercellular Junctions / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000378:metabolism; D020033:Protein Isoforms; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013552:Swine; D013569:Synapses / Q000378:metabolism; D014018:Tissue Distribution
D048868:Adaptor Proteins, Signal Transducing; C114672:Lin7c protein, mouse; D008565:Membrane Proteins; C477071:Mpp4 protein, mouse; D020033:Protein Isoforms; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C499979:Mpp5 protein, mouse