Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

Lelli, Andrea; Michel, Vincent; Monvel, Jacques Boutet de; Cortese, Matteo; Grau, Montserrat Bosch; Aghaie, Asadollah; Perfettini, Isabelle; Dupont, Typhaine; Avan, Paul; El-Amraoui, Aziz; Petit, Christine

doi:10.1083/jcb.201509017

Cited by 58 publications

(71 citation statements)

References 60 publications

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“…A recent study demonstrated severe defects in stereocilia shape and size in MYO3A Ϫ / Ϫ MYO3B Ϫ / Ϫ double knock-out mice (27). On embryonic stage 16.5 of the double knock-out mice, the cochlear hair bundles showed abnormal shape and exaggerated elongation.…”

Section: Discussionmentioning

confidence: 97%

“…The findings from recent MYO3 studies (25,27,32,34) and an overall growing interest in the function of myosins in actinbased protrusions (8,39,46) demanded a systematic study of the functional differences of MYO3 motor and tail domains. Our results highlight the enhanced motor activity of human MYO3A compared with MYO3B, which correlates with its enhanced ability to localize to actin protrusion tips as well as induce the formation and elongation of actin protrusions.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in the absence of MYO3A, the stereocilia elongate abnormally in early development, and because the ultrastructure is perturbed, they are more likely to degenerate as an adult. It should be noted that length regulation in stereocilia is a highly complex process that involves many different players, including multiple unconventional myosins and their binding partners (7,8,27). Indeed, a recent study has shown that MYO3 isoforms are capable of elongating or restricting actin protrusion length depending upon the presence of its specific cargo (ESPN1 or ESPNL) (32).…”

Section: Discussionmentioning

confidence: 99%

“…MYO3B contains a much shorter tail, which includes THD1, but lacks THD2 as well as a large portion of the MYO3A tail with unknown function. Previous reports have hypothesized that MYO3A and MYO3B may have overlapping functions, but MYO3B can only partially compensate for MYO3A (26,27). Thus it is critically important to reveal functional differences between the human isoforms to determine how the loss of MYO3A leads to deafness.…”

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confidence: 99%

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Impact of the Motor and Tail Domains of Class III Myosins on Regulating the Formation and Elongation of Actin Protrusions

Raval

Quintero

Weck

et al. 2016

Journal of Biological Chemistry

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Class III myosins (MYO3A and MYO3B) are proposed to function as transporters as well as length and ultrastructure regulators within stable actin-based protrusions such as stereocilia and calycal processes. MYO3A differs from MYO3B in that it contains an extended tail domain with an additional actin-binding motif. We examined how the properties of the motor and tail domains of human class III myosins impact their ability to enhance the formation and elongation of actin protrusions. Direct examination of the motor and enzymatic properties of human MYO3A and MYO3B revealed that MYO3A is a 2-fold faster motor with enhanced ATPase activity and actin affinity. A chimera in which the MYO3A tail was fused to the MYO3B motor demonstrated that motor activity correlates with formation and elongation of actin protrusions. We demonstrate that removal of individual exons (30-34) in the MYO3A tail does not prevent filopodia tip localization but abolishes the ability to enhance actin protrusion formation and elongation in COS7 cells. Interestingly, our results demonstrate that MYO3A slows filopodia dynamics and enhances filopodia lifetime in COS7 cells. We also demonstrate that MYO3A is more efficient than MYO3B at increasing formation and elongation of stable microvilli on the surface of cultured epithelial cells. We propose that the unique features of MYO3A, enhanced motor activity, and an extended tail with tail actin-binding motif, allow it to play an important role in stable actin protrusion length and ultrastructure maintenance.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Impact of the Motor and Tail Domains of Class III Myosins on Regulating the Formation and Elongation of Actin Protrusions

Raval

Quintero

Weck

et al. 2016

Journal of Biological Chemistry

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“…While myosin XVa is necessary to elongate stereocilia, increasing stereocilia width depends on myosin IIIa and its paralog myosin IIIb as mice lacking both proteins have longer, thinner stereocilia [55]. Myosin IIIa and myosin IIIb also localize to stereocilia tips along with their binding partner, espin-1, which is the longest splice isoform produced from the transcriptionally regulated Espn gene.…”

Section: Development Of Stereociliamentioning

confidence: 99%

Stereocilia morphogenesis and maintenance through regulation of actin stability

McGrath

Roy

Perrin

2017

Seminars in Cell & Developmental Biology

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Stereocilia are actin-based protrusions on auditory and vestibular sensory cells that are required for hearing and balance. They convert physical force from sound, head movement or gravity into an electrical signal, a process that is called mechanoelectrical transduction. This function depends on the ability of sensory cells to grow stereocilia of defined lengths. These protrusions form a bundle with a highly precise geometry that is required to detect nanoscale movements encountered in the inner ear. Congenital or progressive stereocilia degeneration causes hearing loss. Thus, understanding stereocilia hair bundle structure, development, and maintenance is pivotal to understanding the pathogenesis of deafness. Stereocilia cores are made from a tightly packed array of parallel, crosslinked actin filaments, the length and stability of which are regulated in part by myosin motors, actin crosslinkers and capping proteins. This review aims to describe stereocilia actin regulation in the context of an emerging “tip turnover” model where actin assembles and disassembles at stereocilia tips while the remainder of the core is exceptionally stable.

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Segmental Duplications and CNVs

BALARESQUE,

DELEHELLE

2023

Function and Evolution of Repeated DNA Sequences

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Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

Abstract: Analysis of mice deficient for myosin IIIa and myosin IIIb shows that class III myosins limit the elongation of stereocilia and of subsequently regressing microvilli, thus contributing to the early hair bundle shaping.

Cited by 58 publications

References 60 publications

Impact of the Motor and Tail Domains of Class III Myosins on Regulating the Formation and Elongation of Actin Protrusions

Impact of the Motor and Tail Domains of Class III Myosins on Regulating the Formation and Elongation of Actin Protrusions

Stereocilia morphogenesis and maintenance through regulation of actin stability

Segmental Duplications and CNVs

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