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Kerstin Nagel-Wolfrum, Mirjana Becker, Tobias Goldmann, Christina Müller, Jan Vetter, Uwe Wolfrum; USH1C Transcripts And Harmonin Protein Expression In Human Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):45.
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The human Usher syndrome (USH) is the most frequent cause of inherited combined deaf-blindness. 9 identified USH genes encode proteins of diverse protein families. All known USH1/2 proteins are organized in protein networks and the USH1C scaffold protein harmonin serves as one of the key network organizers. USH1C is expressed in various alternative spliced variants grouped into three classes, based on the modular composition of their protein domains. We investigated the expression profiles of harmonin isoforms in the human retina and analyzed harmonin's localization in primate retinas.
We analyzed the expression of harmonin isoforms in human retina by RT-PCR and Western blots, and harmonin localization in primate retina by correlative high resolution immunofluorescence and immunoelectron microscopy applying molecular markers.
Here we show expression of all harmonin classes (a-c) in the human retina. Subcellular localization of harmonin demonstrated differential harmonin expression in primate rod and cone synapses. In addition we found harmonin in adhesion complexes of the outer limiting membrane in photoreceptor cells, but not in Müller cells, in inner and outer segments of photoreceptor cells, but not in the connecting cilium or in the periciliary protein complex, where a USH protein network was previously described. Co-staining with antibodies against harmonin and cone-specific markers as well as immunoelectron microscopy revealed harmonin expression in outer segments of primate rod photoreceptor cells but not in cones.
Present data reveal that harmonin isoforms of all classes are expressed in the human retina. We assume that the scaffold harmonin organizes membrane associated networks at the outer limiting membrane, in the outer segment of rods and in the synaptic terminals predominantly in cones. Defects in harmonin may cause disturbance of these protein networks resulting in the retinal phenotype of USH1C.
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