Mutations of the mouse ELMO domain containing 1 gene (Elmod1) link small GTPase signaling to actin cytoskeleton dynamics in hair cell stereocilia.

PloS One
Kenneth R JohnsonLeona H Gagnon

Abstract

Stereocilia, the modified microvilli projecting from the apical surfaces of the sensory hair cells of the inner ear, are essential to the mechanoelectrical transduction process underlying hearing and balance. The actin-filled stereocilia on each hair cell are tethered together by fibrous links to form a highly patterned hair bundle. Although many structural components of hair bundles have been identified, little is known about the signaling mechanisms that regulate their development, morphology, and maintenance. Here, we describe two naturally occurring, allelic mutations that result in hearing and balance deficits in mice, named roundabout (rda) and roundabout-2J (rda(2J)). Positional cloning identified both as mutations of the mouse ELMO domain containing 1 gene (Elmod1), a poorly characterized gene with no previously reported mutant phenotypes. The rda mutation is a 138 kb deletion that includes exons 1-5 of Elmod1, and rda(2J) is an intragenic duplication of exons 3-8 of Elmod1. The deafness associated with these mutations is caused by cochlear hair cell dysfunction, as indicated by conspicuous elongations and fusions of inner hair cell stereocilia and progressive degeneration of outer hair cell stereocilia. Mammalian ELMO-...Continue Reading

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Citations

Mar 17, 2016·Journal of the Association for Research in Otolaryngology : JARO·Kevin K OhlemillerPatricia M Gagnon
Apr 20, 2016·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Kenneth R JohnsonBo Chang
Apr 8, 2015·Journal of Proteome Research·Fay ProbertI Jane Cox
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Oct 13, 2018·Physiological Genomics·Marius Catalin StaiculescuJessica E Wagenseil
Feb 14, 2014·PloS One·Ashutosh K PandeyRobert W Williams
Aug 16, 2016·G3 : Genes - Genomes - Genetics·Joel LavinskyRick A Friedman
Jul 22, 2019·Journal of Molecular Neuroscience : MN·Mohammad MiryounesiSoudeh Ghafouri-Fard
Feb 18, 2021·Molecular Biology of the Cell·Rachel E TurnRichard A Kahn
Mar 13, 2014·Journal of Cell Science·Takehiko UeyamaNaoaki Saito
Jul 22, 2021·The Journal of Cell Biology·Kilian TrilletJulie Gavard

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Methods Mentioned

BETA
GTPases
GTPase
nucleotide exchange
scanning electron microscopy
PCR
genotyping
in vitro transcription

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