Localization of PDZD7 to the Stereocilia Ankle-Link Associates this Scaffolding Protein with the Usher Syndrome Protein Network

• DOI: 10.1523/jneurosci.3071-12.2012
• Publication Date: 2012-10-10T18:54:32Z
• Authors: M'hamed Grati; Jung-Bum Shin; Michael D. Weston; James Green; Manzoor A. Bhat; Peter G. Gillespie; Bechara Kachar
• Keywords: Usher syndrome; Stereocilia (inner ear); PDZ domain; HEK 293 cells

Usher syndrome is the leading cause of genetic deaf–blindness. Monoallelic mutations in PDZD7 increase severity type II caused by USH2A and GPR98 , which respectively encode usherin GPR98. PDZ domain-containing 7 protein (PDZD7) a paralog scaffolding proteins harmonin whirlin, are implicated 1 2 syndromes. While have been reported to form hair cell stereocilia ankle-links, localizes upper tip-link density whirlin both tip ankle-link regions. Here, we used mass spectrometry show that expressed chick at comparable molecular abundance We also immunofluorescence overexpression tagged rat mouse cells region, overlapping with usherin, Finally, LLC-PK1 cytosolic domains can bind PDZD7. These observations consistent being modifier candidate gene for USH2, suggest second component complex.