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III类肌球蛋白通过限制微绒毛和静纤毛的生长来塑造听觉毛束。

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

作者信息

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

机构信息

Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, 75724 Paris, Cedex 15, France Unité Mixte de Recherche UMRS1120, Institut National de la Santé et de la Recherche Médicale, 75015 Paris, France Sorbonne Universités, Université Pierre et Marie Curie (UPMC Paris VI), Complexité du Vivant, 75005 Paris, France.

Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, 75724 Paris, Cedex 15, France Unité Mixte de Recherche UMRS1120, Institut National de la Santé et de la Recherche Médicale, 75015 Paris, France Sorbonne Universités, Université Pierre et Marie Curie (UPMC Paris VI), Complexité du Vivant, 75005 Paris, France Syndrome de Usher et Autres Atteintes Rétino-Cochléaires, Institut de la Vision, 75012 Paris, France.

出版信息

J Cell Biol. 2016 Jan 18;212(2):231-44. doi: 10.1083/jcb.201509017. Epub 2016 Jan 11.

DOI:10.1083/jcb.201509017
PMID:26754646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4738386/
Abstract

The precise architecture of hair bundles, the arrays of mechanosensitive microvilli-like stereocilia crowning the auditory hair cells, is essential to hearing. Myosin IIIa, defective in the late-onset deafness form DFNB30, has been proposed to transport espin-1 to the tips of stereocilia, thereby promoting their elongation. We show that Myo3a(-/-)Myo3b(-/-) mice lacking myosin IIIa and myosin IIIb are profoundly deaf, whereas Myo3a-cKO Myo3b(-/-) mice lacking myosin IIIb and losing myosin IIIa postnatally have normal hearing. Myo3a(-/-)Myo3b(-/-) cochlear hair bundles display robust mechanoelectrical transduction currents with normal kinetics but show severe embryonic abnormalities whose features rapidly change. These include abnormally tall and numerous microvilli or stereocilia, ungraded stereocilia bundles, and bundle rounding and closure. Surprisingly, espin-1 is properly targeted to Myo3a(-/-)Myo3b(-/-) stereocilia tips. Our results uncover the critical role that class III myosins play redundantly in hair-bundle morphogenesis; they unexpectedly limit the elongation of stereocilia and of subsequently regressing microvilli, thus contributing to the early hair bundle shaping.

摘要

毛束是由机械敏感的微绒毛样静纤毛组成的阵列，覆盖在听觉毛细胞上，其精确结构对听力至关重要。肌球蛋白IIIa在迟发性耳聋形式DFNB30中存在缺陷，有人提出它将espin-1转运到静纤毛的尖端，从而促进其伸长。我们发现，缺乏肌球蛋白IIIa和肌球蛋白IIIb的Myo3a(-/-)Myo3b(-/-)小鼠严重耳聋，而缺乏肌球蛋白IIIb且在出生后失去肌球蛋白IIIa的Myo3a-cKO Myo3b(-/-)小鼠听力正常。Myo3a(-/-)Myo3b(-/-)耳蜗毛束表现出具有正常动力学的强大机械电转导电流，但显示出严重的胚胎异常，其特征迅速变化。这些异常包括异常高大且数量众多的微绒毛或静纤毛、未分级的静纤毛束以及束的变圆和闭合。令人惊讶的是，espin-1能正确地靶向到Myo3a(-/-)Myo3b(-/-)静纤毛的尖端。我们的结果揭示了III类肌球蛋白在毛束形态发生中发挥的冗余关键作用；它们意外地限制了静纤毛以及随后退化的微绒毛的伸长，从而有助于早期毛束的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/a46902eeb1c0/JCB_201509017_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/bc2e10c4d7dc/JCB_201509017_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/bb9f830739ec/JCB_201509017_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/b4874518783d/JCB_201509017_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/fe2d067b838e/JCB_201509017_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/4ff7781f2f99/JCB_201509017_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/ca739856df9f/JCB_201509017_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/e2bb66a287c9/JCB_201509017_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/94aa17c1f957/JCB_201509017_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/a46902eeb1c0/JCB_201509017_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/bc2e10c4d7dc/JCB_201509017_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/bb9f830739ec/JCB_201509017_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/b4874518783d/JCB_201509017_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/fe2d067b838e/JCB_201509017_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/4ff7781f2f99/JCB_201509017_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/ca739856df9f/JCB_201509017_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/e2bb66a287c9/JCB_201509017_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/94aa17c1f957/JCB_201509017_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5609/4738386/a46902eeb1c0/JCB_201509017_Fig9.jpg

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