Journal Article

Interactions in the network of Usher syndrome type 1 proteins

Avital Adato, Vincent Michel, Yoshiaki Kikkawa, Jan Reiners, Kumar N. Alagramam, Dominique Weil, Hiromichi Yonekawa, Uwe Wolfrum, Aziz El-Amraoui and Christine Petit

in Human Molecular Genetics

Volume 14, issue 3, pages 347-356
Published in print February 2005 | ISSN: 0964-6906
Published online December 2004 | e-ISSN: 1460-2083 | DOI:
Interactions in the network of Usher syndrome type 1 proteins

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Defects in myosin VIIa, harmonin (a PDZ domain protein), cadherin 23, protocadherin 15 and sans (a putative scaffolding protein), underlie five forms of Usher syndrome type I (USH1). Mouse mutants for all these proteins exhibit disorganization of their hair bundle, which is the mechanotransduction receptive structure of the inner ear sensory cells, the cochlear and vestibular hair cells. We have previously demonstrated that harmonin interacts with cadherin 23 and myosin VIIa. Here we address the extent of interactions between the five known USH1 proteins. We establish the previously suggested sans–harmonin interaction and find that sans also binds to myosin VIIa. We show that sans can form homomeric structures and that harmonin b can interact with all harmonin isoforms. We reveal that harmonin also binds to protocadherin 15. Molecular characterization of these interactions indicates that through its binding to four of the five USH1 proteins, the first PDZ domain (PDZ1) of harmonin plays a central role in this network. We localize sans in the apical region of cochlear and vestibular hair cell bodies underneath the cuticular plate. In contrast to the other four known USH1 proteins, no sans labeling was detected within the stereocilia. We propose that via its binding to myosin VIIa and/or harmonin, sans controls the hair bundle cohesion and proper development by regulating the traffic of USH1 proteins en route to the stereocilia.

Journal Article.  7182 words.  Illustrated.

Subjects: Genetics and Genomics

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