CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell stereocilia in a molecular complex with radixin, taperin, and myosin VI

Felipe T. Salles, Leonardo R. Andrade, Soichi Tanda, M'hamed Grati, Kathleen L. Plona, Leona H. Gagnon, Kenneth R. Johnson, Bechara Kachar, Mark A. Berryman

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Chloride intracellular channel 5 protein (CLIC5) was originally isolated from microvilli in complex with actin binding proteins including ezrin, a member of the Ezrin-Radixin-Moesin (ERM) family of membrane-cytoskeletal linkers. CLIC5 concentrates at the base of hair cell stereocilia and is required for normal hearing and balance in mice, but its functional significance is poorly understood. This study investigated the role of CLIC5 in postnatal development and maintenance of hair bundles. Confocal and scanning electron microscopy of CLIC5-deficient jitterbug (jbg) mice revealed progressive fusion of stereocilia as early as postnatal day 10. Radixin (RDX), protein tyrosine phosphatase receptor Q (PTPRQ), and taperin (TPRN), deafness-associated proteins that also concentrate at the base of stereocilia, were mislocalized in fused stereocilia of jbg mice. TPRQ and RDX were dispersed even prior to stereocilia fusion. Biochemical assays showed interaction of CLIC5 with ERM proteins, TPRN, and possibly myosin VI (MYO6). In addition, CLIC5 and RDX failed to localize normally in fused stereocilia of MYO6 mutant mice. Based on these findings, we propose a model in which these proteins work together as a complex to stabilize linkages between the plasma membrane and subjacent actin cytoskeleton at the base of stereocilia. Published 2013 Wiley Periodicals, Inc. This article is a US government work and, as such, is in the public domain in the United States of America.

Original languageEnglish (US)
Pages (from-to)61-78
Number of pages18
JournalCytoskeleton
Volume71
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Fingerprint

Stereocilia
Actin Cytoskeleton
Membrane Proteins
Proteins
myosin VI
radixin
CLC-5 chloride channel
Microfilament Proteins
Protein Tyrosine Phosphatases
Public Sector
Deafness
Microvilli
Electron Scanning Microscopy
Hearing
Maintenance
Cell Membrane

Keywords

  • Chloride intracellular channel 5 (CLIC5)
  • Cytoskeleton
  • Deafness
  • Ezrin-radixin-moesin (ERM)
  • Hair cell
  • Myosin VI (MYO6)
  • PTPRQ
  • Radixin
  • Stereocilia
  • Taperin

ASJC Scopus subject areas

  • Cell Biology
  • Structural Biology

Cite this

Salles, F. T., Andrade, L. R., Tanda, S., Grati, M., Plona, K. L., Gagnon, L. H., ... Berryman, M. A. (2014). CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell stereocilia in a molecular complex with radixin, taperin, and myosin VI. Cytoskeleton, 71(1), 61-78. https://doi.org/10.1002/cm.21159

CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell stereocilia in a molecular complex with radixin, taperin, and myosin VI. / Salles, Felipe T.; Andrade, Leonardo R.; Tanda, Soichi; Grati, M'hamed; Plona, Kathleen L.; Gagnon, Leona H.; Johnson, Kenneth R.; Kachar, Bechara; Berryman, Mark A.

In: Cytoskeleton, Vol. 71, No. 1, 01.2014, p. 61-78.

Research output: Contribution to journalArticle

Salles, FT, Andrade, LR, Tanda, S, Grati, M, Plona, KL, Gagnon, LH, Johnson, KR, Kachar, B & Berryman, MA 2014, 'CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell stereocilia in a molecular complex with radixin, taperin, and myosin VI', Cytoskeleton, vol. 71, no. 1, pp. 61-78. https://doi.org/10.1002/cm.21159
Salles, Felipe T. ; Andrade, Leonardo R. ; Tanda, Soichi ; Grati, M'hamed ; Plona, Kathleen L. ; Gagnon, Leona H. ; Johnson, Kenneth R. ; Kachar, Bechara ; Berryman, Mark A. / CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell stereocilia in a molecular complex with radixin, taperin, and myosin VI. In: Cytoskeleton. 2014 ; Vol. 71, No. 1. pp. 61-78.
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abstract = "Chloride intracellular channel 5 protein (CLIC5) was originally isolated from microvilli in complex with actin binding proteins including ezrin, a member of the Ezrin-Radixin-Moesin (ERM) family of membrane-cytoskeletal linkers. CLIC5 concentrates at the base of hair cell stereocilia and is required for normal hearing and balance in mice, but its functional significance is poorly understood. This study investigated the role of CLIC5 in postnatal development and maintenance of hair bundles. Confocal and scanning electron microscopy of CLIC5-deficient jitterbug (jbg) mice revealed progressive fusion of stereocilia as early as postnatal day 10. Radixin (RDX), protein tyrosine phosphatase receptor Q (PTPRQ), and taperin (TPRN), deafness-associated proteins that also concentrate at the base of stereocilia, were mislocalized in fused stereocilia of jbg mice. TPRQ and RDX were dispersed even prior to stereocilia fusion. Biochemical assays showed interaction of CLIC5 with ERM proteins, TPRN, and possibly myosin VI (MYO6). In addition, CLIC5 and RDX failed to localize normally in fused stereocilia of MYO6 mutant mice. Based on these findings, we propose a model in which these proteins work together as a complex to stabilize linkages between the plasma membrane and subjacent actin cytoskeleton at the base of stereocilia. Published 2013 Wiley Periodicals, Inc. This article is a US government work and, as such, is in the public domain in the United States of America.",
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AU - Andrade, Leonardo R.

AU - Tanda, Soichi

AU - Grati, M'hamed

AU - Plona, Kathleen L.

AU - Gagnon, Leona H.

AU - Johnson, Kenneth R.

AU - Kachar, Bechara

AU - Berryman, Mark A.

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