Stereocilia in hair cells of the inner ear are responsible for several functions, such as hearing and vestibular sense. They contain a cystoskeletal scaffold that consists of a parallel actin bundle and a number of actin-bundling factors, such as espins, that have been shown to be mutated in deafness and vestibular dysfunction. Espins show no obvious resemblance to other actin-bundling proteins in vertebrates and, in addition, the different espin isoforms are all transcribed from a single gene. James Bartles and colleagues had previously shown that a short C-terminal ‘peptide’ that is shared by all espin isoforms – the so called actin-bundling module (ABM) – is sufficient for actin bundling in vitro; but this raises the question why different espin isoforms exist. In this study (p. 1306), the authors characterise the additional actin-filament-binding site (xAB), a 23 amino acid stretch located upstream of ABM that is present in the large isoforms espin 1 and espin 2. They report that xAB is constitutively active in espin 2 and increases the size and stability of actin bundles formed in vitro. By contrast, espin 1 contains an N-terminal ankyrin-repeat-binding (ARB) region that interacts with a peptide stretch near the xAB region, thus inhibiting its actin-bundling activity. Accordingly, when the authors delete ARB, they observe xAB-mediated actin bundling. Interestingly, upon close inspection of the ARB region – which is conserved among the espins – resemblance to the tail-homology region of myosin III (MYO3) became apparent, prompting an investigation into its possible role in the regulation of espin1. Indeed, the authors show that a synthetic MYO3 peptide encompassing this region can bind to espin 1 and release the ankyrin repeat domain-induced autoinhibition. These findings suggest that the additional actin-binding site in espin 1 is activated in a MYO3-dependent and, thus, localised manner in stereocilia.
IN THIS ISSUE|
15 March 2014
Localised activation of espins in stereocilia
Online ISSN: 1477-9137
Print ISSN: 0021-9533
© 2014. Published by The Company of Biologists Ltd
2014
J Cell Sci (2014) 127 (6): e0604.
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Localised activation of espins in stereocilia. J Cell Sci 15 March 2014; 127 (6): e0604. doi:
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