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 Weston, James Green, Manzoor A. Bhat, Peter G. Gillespie, Bechara Kachar

Research output: Contribution to journalArticle

33 Citations (Scopus)

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

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Usher Syndromes
Stereocilia
PDZ Domains
Ankle
Proteins
Modifier Genes
LLC-PK1 Cells
Mutation
Blindness
Fluorescent Antibody Technique
Mass Spectrometry

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Localization of PDZD7 to the stereocilia ankle-link associates this scaffolding protein with the usher syndrome protein network. / Grati, M'hamed; Shin, Jung Bum; Weston, Michael; Green, James; Bhat, Manzoor A.; Gillespie, Peter G.; Kachar, Bechara.

In: Journal of Neuroscience, Vol. 32, No. 41, 10.10.2012, p. 14288-14293.

Research output: Contribution to journalArticle

Grati, M'hamed ; Shin, Jung Bum ; Weston, Michael ; Green, James ; Bhat, Manzoor A. ; Gillespie, Peter G. ; Kachar, Bechara. / Localization of PDZD7 to the stereocilia ankle-link associates this scaffolding protein with the usher syndrome protein network. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 41. pp. 14288-14293.
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