PHR1, an integral membrane protein of the inner ear sensory cells, directly interacts with myosin 1c and myosin VIIa.
By using the yeast two-hybrid technique, we identified a candidate protein ligand of the myosin 1c tail, PHR1, and found that this protein can also bind to the myosin VIIa tail. PHR1 is an integral membrane protein that contains a pleckstrin homology (PH) domain. Myosin 1c and myosin VIIa are two unconventional myosins present in the inner ear sensory cells. We showed that PHR1 immunoprecipitates with either myosin tail by using protein extracts from cotransfected HEK293 cells. In vitro binding assays confirmed that PHR1 directly interacts with these two myosins. In both cases the binding involves the PH domain. In vitro interactions between PHR1 and the myosin tails were not affected by the presence or absence of Ca2+ and calmodulin. Finally, we found that PHR1 is able to dimerise. As PHR1 is expressed in the vestibular and cochlear sensory cells, its direct interactions with the myosin 1c and VIIa tails are likely to play a role in anchoring the actin cytoskeleton to the plasma membrane of these cells. Moreover, as both myosins have been implicated in the mechanotransduction slow adaptation process that takes place in the hair bundles, we propose that PHR1 is also involved in this process.
Etournay
Raphaël
R
Unité de Génétique des Déficits Sensoriels, INSERM U587, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France.
El-Amraoui
Aziz
A
Bahloul
Amel
A
Blanchard
Stéphane
S
Roux
Isabelle
I
Pézeron
Guillaume
G
Michalski
Nicolas
N
Daviet
Laurent
L
Hardelin
Jean-Pierre
JP
Legrain
Pierre
P
Petit
Christine
C
D000818:Animals; D002460:Cell Line; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D006199:Hair Cells, Auditory, Inner / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D024461:Myosin Type I; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics / Q000378:metabolism*
C000631455:MYO7A protein, human; D008565:Membrane Proteins; C470422:Myo1c protein, mouse; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; C485943:Plekhb1 protein, mouse; D024461:Myosin Type I; D009218:Myosins; D004398:Dyneins