Human Molecular Genetics Advance Access published online on March 6, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl047
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1 The Netherlands Institute for Neurosciences, Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands
* To whom correspondence should be addressed. 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) where it might be involved in OLM integrity. 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. Scanning laser ophthalmology revealed no retinal degeneration. The minor morphological effects suggest that Mpp4 is a candidate gene for mild retinopathies only. 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 electroretinograph. These findings suggest that Mpp4 coordinates Psd95/Veli3 assembly and maintenance at synaptic membranes. Mpp4 is a critical recruitment factor to organize scaffolds at the photoreceptor synapse and is likely to be associated with synaptic plasticity and protein complex transport.
Received November 1, 2005
Revised February 24, 2006
Accepted March 2, 2006
Article
Mpp4 recruits Psd95 and Veli3 towards the photoreceptor synapse
Wendy M. Aartsen 1,
Albena Kantardzhieva 1,
Jan Klooster 1,
Agnes G.S.H. van Rossum 1,
Serge A. van de Pavert 1,
Inge Versteeg 1,
Bob Nunes Cardozo 1,
Felix Tonagel 2,
Susanne C. Beck 2,
Naoyuki Tanimoto 2,
Mathias W. Seeliger 2,
and
Jan Wijnholds 3 *
2 Retinal Electrodiagnostics Research Group, Department of Ophthalmology, University of Tübingen, Schleichstr. 12-16, 72076 Tübingen, Germany
3 Department of Neuromedical Genetics, The Netherlands Institute for Neurosciences, Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands
Jan Wijnholds, E-mail: j.wijnholds{at}nin.knaw.nl
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