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W.M. Aartsen, A. Kantardzhieva, J. Klooster, A.G. S. H. van Rossum, I. Versteeg, S.C. Beck, N. Tanimoto, M.W. Seeliger; Mpp4 Recruits Psd95 and Veli3 Towards the Photoreceptor Synapse . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4582.
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© ARVO (1962-2015); The Authors (2016-present)
Membrane–associated guanylate kinase (MAGUK) proteins function as scaffold proteins contributing to cell polarity and organizing signal transducers at the neuronal synapse membrane. The MAGUK protein Mpp4 is located in the retinal outer plexiform layer (OPL) at the presynaptic plasma membrane and presynaptic vesicles of photoreceptors. Additionally, it is located at the outer limiting membrane (OLM). So in the photoreceptor, Mpp4 might be involved in OLM integrity and in the organization of presynaptic scaffolds and signal transducers.
Mpp4 knockout and wild–type retinas were histological, immuno–histochemical and electron microscopic examined at 1, 3, 6 and 12 months of age. The structural and functional integrity of the Mpp4 knockout retina was investigated and compared to wild–type retinas using scanning laser ophthalmology (SLO) and electroretinography (ERG) at 9 and 18 months of age. Immunoprecipitaion was used to study the interaction between Mpp4 and the MAGUK proteins Psd95, Veli3, Dlg and Cask.
In the Mpp4 knockout mice, loss of Mpp4 function only sporadically causes photoreceptor displacement, without changing the Crumbs (Crb) protein complex at the OLM, adherens junctions or synapse structure. SLO revealed no retinal degeneration. At the OPL, Mpp4 is essential for correct localization of Psd95 and Veli3 at the presynaptic photoreceptor membrane. Psd95 labeling is absent of presynaptic membranes in both rods and cones but still present in cone basal contacts and dendritic contacts. Total retinal Psd95 protein levels are significantly reduced which suggests Mpp4 to be involved in Psd95 turnover, whereas Veli3 proteins levels are not changed. These protein changes in the photoreceptor synapse did not result in an altered ERG.
These data suggest that Mpp4 is a candidate gene for mild retinopathies only. Further results suggest that Mpp4 coordinates Psd95/Veli3 assembly and maintenance at synaptic membranes. Mpp4 is a critical recruitment factor to organize signal transducers at the photoreceptor synapse and is likely to be associated with synaptic plasticity and protein complex transport.
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