Mpp4 recruits Psd95 and Veli3 towards the photoreceptor synapse

Hum Mol Genet. 2006 Apr 15;15(8):1291-302. doi: 10.1093/hmg/ddl047. Epub 2006 Mar 6.

Abstract

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Membrane / metabolism
  • Disks Large Homolog 4 Protein
  • Down-Regulation
  • Electroretinography
  • Guanylate Kinases
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / ultrastructure
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Models, Genetic
  • Nerve Tissue Proteins / metabolism
  • Photoreceptor Cells / metabolism*
  • Retina / metabolism
  • Retina / ultrastructure
  • Retinal Diseases / genetics
  • Retinal Diseases / metabolism
  • Signal Transduction
  • Synapses / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Crb1 protein, mouse
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Lin7c protein, mouse
  • Membrane Proteins
  • Mpp4 protein, mouse
  • Nerve Tissue Proteins
  • Guanylate Kinases