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Originally published In Press as doi:10.1074/jbc.M004393200 on July 10, 2000
J. Biol. Chem., Vol. 275, Issue 38, 29654-29659, September 22, 2000
Unconventional Myosin VIIA Is a Novel A-kinase-anchoring
Protein*
Polonca
Küssel-Andermann ,
Aziz
El-Amraoui ,
Saaid
Safieddine ,
Jean-Pierre
Hardelin ,
Sylvie
Nouaille ,
Jacques
Camonis§, and
Christine
Petit ¶
From the Unité de Génétique des
Déficits Sensoriels, CNRS URA 1968, 25 rue du Dr. Roux, Institut
Pasteur, 75724 Paris cedex 15, France and § INSERM U248,
Institut Curie, 75248 Paris cedex 05, France
To gain an insight into the cellular function of
the unconventional myosin VIIA, we sought proteins interacting with its
tail region, using the yeast two-hybrid system. Here we report on one of the five candidate interactors we identified, namely the type I
regulatory subunit (RI ) of protein kinase A. The interaction of
RI with myosin VIIA tail was demonstrated by coimmunoprecipitation from transfected HEK293 cells. Analysis of deleted constructs in the
yeast two-hybrid system showed that the interaction of myosin VIIA with
RI involves the dimerization domain of RI . In vitro
binding assays identified the C-terminal "4.1, ezrin, radixin,
moesin" (FERM)-like domain of myosin VIIA as the interacting domain.
In humans and mice, mutations in the myosin VIIA
gene underlie hereditary hearing loss, which may or may not be
associated with visual deficiency. Immunohistofluorescence revealed
that myosin VIIA and RI are coexpressed in the outer hair cells of the cochlea and rod photoreceptor cells of the retina. Our results strongly suggest that myosin VIIA is a novel protein kinase A-anchoring protein that targets protein kinase A to definite subcellular sites of
these sensory cells.
*
This work was supported by European Community Grant
QLG2-CT-1999-00988; grants from Retina-France, A. and M. Suchert, and Forschung contra Blindheit-Initiative Usher Syndrom; and a donation from C. and J-P. Bernais.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
¶
To whom correspondence should be addressed. Tel.: 33 1 45 68 88 50 or 33 1 45 68 88 90; Fax: 33 1 45 67 69 78; E-mail:
cpetit@pasteur.fr.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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