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JH Brandstatter, O Dick, T Böckers; The Molecular Composition Of Postsynaptic Densities At Glutamatergic Synapses In Rat Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1968.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:The postsynaptic density (PSD), an ultrastructural thickening of the postsynaptic membrane at synapses, comprises a macromolecular signaling complex. Recently, a family of multidomain proteins called ProSAPs (proline-rich synapse-associated proteins) or Shanks, has been identified as components of the PSD of glutamatergic synapses (Böckers et al., 1999, J. Neurosci. 19: 6506-6518; Naisbitt et al., 1999, Neuron 23: 569-582; Tu et al., 1999, Neuron 23: 583-592). ProSAP/Shank proteins are scaffolding proteins that seem to interact with metabotropic glutamate receptors, NMDA receptors, possibly AMPA receptors, and with the cytoskeleton. Methods:Using immunocytochemistry we examined in single- and double-labeling experiments, the synaptic distribution and the ultrastructural localization of ProSAP1 (= Shank2) at the synapses of rat retina, by confocal and immunoelectron microscopy. Results:Light microscopically, strong punctate immunofluorescence was found for ProSAP1 in the outer (OPL) and the inner (IPL) plexiform layers of the retina. Electron microscopy showed that ProSAP1 is present postsynaptic to ribbon synapses of photoreceptors and bipolar cells; in the processes of bipolar, horizontal and amacrine cells known to express different kinds of ionotropic (iGluRs) and metabotropic glutamate receptors (mGluRs). The double-labeling experiments confirmed that ProSAP1 is present in the PSD of glutamatergic synapses but not of GABAergic and glycinergic synapes. At glutamatergic synapses, ProSAP1 was co-expressed with PSD-95 and Homer, two proteins involved in the organization of the PSD of synapses containing NMDA receptors and mGluRs, respectively. No significant co-expression was found between ProSAP1 and GRIP, a protein known to be involved in the synaptic targeting/aggregation of AMPA receptors. Conclusion:The PSD of glutamatergic synapses in the retina comprises a mixture of different types of iGluRs and mGluRs. It is an intriguing possibilty that ProSAP1 acts as a central organizer at the PSD linking different types of glutamate receptors, in particular NMDA and metabotropic glutamate receptors, to each other and to the cytoskeleton.
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