Localization of PDZD7 to the stereocilia ankle-link associates this scaffolding protein with the usher syndrome protein network

M'hamed Grati, Jung Bum Shin, Michael D. Weston, James Green, Manzoor A. Bhat, Peter G. Gillespie, Bechara Kachar

Research output: Contribution to journalArticle

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Abstract

Usher syndrome is the leading cause of genetic deaf-blindness. Monoallelic mutations in PDZD7 increase the severity of Usher type II syndrome caused by mutations in USH2A and GPR98, which respectively encode usherin and GPR98. PDZ domain-containing 7 protein (PDZD7)isaparalogofthe scaffolding proteins harmonin and whirlin, which are implicatedinUsher type1and type2syndromes. While usherin and GPR98 have been reportedtoform hair cell stereocilia ankle-links, harmonin localizestothe stereocilia upper tip-link density and whirlin localizes to both tip and ankle-link regions. Here, we used mass spectrometry to show that PDZD7 is expressed in chick stereocilia at a comparable molecular abundance to GPR98. We also show by immunofluorescence and by overexpression of tagged proteinsin rat and mouse hair cells that PDZD7 localizes to the ankle-link region, overlapping with usherin, whirlin, and GPR98. Finally, we show in LLC-PK1 cells that cytosolic domains of usherin and GPR98 can bind to both whirlin and PDZD7. These observations are consistent with PDZD7 being a modifier and candidate gene for USH2, and suggest that PDZD7 isa second scaffolding component of the ankle-link complex.

Original languageEnglish (US)
Pages (from-to)14288-14293
Number of pages6
JournalJournal of Neuroscience
Volume32
Issue number41
DOIs
StatePublished - Oct 10 2012

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ASJC Scopus subject areas

  • Neuroscience(all)

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