Neuroplastin isoform Np55 is expressed in the stereocilia of outer hair cells and required for normal outer hair cell function

Wei Zheng Zeng, Nicolas Grillet, James B. Dewey, Alix Trouillet, Jocelyn F. Krey, Peter Barr-Gillespie, John S. Oghalai, Ulrich Müller

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Neuroplastin (Nptn) is a member of the Ig superfamily and is expressed in two isoforms, Np55 and Np65. Np65 regulates synaptic transmission but the function of Np55 is unknown. In anN-ethyl-N-nitrosaurea mutagenesis screen, we have now generated a mouse line with an Nptn mutation that causes deafness. We show that Np55 is expressed in stereocilia of outer hair cells (OHCs) but not inner hair cells and affects interactions of stereocilia with the tectorial membrane. In vivo vibrometry demonstrates that cochlear amplification is absent in Nptn mutant mice, which is consistent with the failure of OHC stereocilia to maintain stable interactions with the tectorial membrane. Hair bundles show morphological defects as the mutant mice age and while mechanotransduction currents can be evoked in early postnatal hair cells, cochlea microphonics recordings indicate that mechanon transduction is affected as the mutant mice age. We thus conclude that differential splicing leads to functional diversification of Nptn, where Np55 is essential for OHC function, while Np65 is implicated in the regulation of synaptic function.

Original languageEnglish (US)
Pages (from-to)9201-9216
Number of pages16
JournalJournal of Neuroscience
Volume36
Issue number35
DOIs
StatePublished - Aug 31 2016

Fingerprint

Outer Auditory Hair Cells
Stereocilia
Protein Isoforms
Tectorial Membrane
Cochlea
Inner Auditory Hair Cells
Deafness
Cell Communication
Synaptic Transmission
Mutagenesis
Mutation

Keywords

  • Amplification
  • Deafness
  • Hair cells
  • Inner ear
  • Neuroplastin
  • Tectorial membrane

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Neuroplastin isoform Np55 is expressed in the stereocilia of outer hair cells and required for normal outer hair cell function. / Zeng, Wei Zheng; Grillet, Nicolas; Dewey, James B.; Trouillet, Alix; Krey, Jocelyn F.; Barr-Gillespie, Peter; Oghalai, John S.; Müller, Ulrich.

In: Journal of Neuroscience, Vol. 36, No. 35, 31.08.2016, p. 9201-9216.

Research output: Contribution to journalArticle

Zeng, Wei Zheng ; Grillet, Nicolas ; Dewey, James B. ; Trouillet, Alix ; Krey, Jocelyn F. ; Barr-Gillespie, Peter ; Oghalai, John S. ; Müller, Ulrich. / Neuroplastin isoform Np55 is expressed in the stereocilia of outer hair cells and required for normal outer hair cell function. In: Journal of Neuroscience. 2016 ; Vol. 36, No. 35. pp. 9201-9216.
@article{95a3015df18547b1b21721a614fec842,
title = "Neuroplastin isoform Np55 is expressed in the stereocilia of outer hair cells and required for normal outer hair cell function",
abstract = "Neuroplastin (Nptn) is a member of the Ig superfamily and is expressed in two isoforms, Np55 and Np65. Np65 regulates synaptic transmission but the function of Np55 is unknown. In anN-ethyl-N-nitrosaurea mutagenesis screen, we have now generated a mouse line with an Nptn mutation that causes deafness. We show that Np55 is expressed in stereocilia of outer hair cells (OHCs) but not inner hair cells and affects interactions of stereocilia with the tectorial membrane. In vivo vibrometry demonstrates that cochlear amplification is absent in Nptn mutant mice, which is consistent with the failure of OHC stereocilia to maintain stable interactions with the tectorial membrane. Hair bundles show morphological defects as the mutant mice age and while mechanotransduction currents can be evoked in early postnatal hair cells, cochlea microphonics recordings indicate that mechanon transduction is affected as the mutant mice age. We thus conclude that differential splicing leads to functional diversification of Nptn, where Np55 is essential for OHC function, while Np65 is implicated in the regulation of synaptic function.",
keywords = "Amplification, Deafness, Hair cells, Inner ear, Neuroplastin, Tectorial membrane",
author = "Zeng, {Wei Zheng} and Nicolas Grillet and Dewey, {James B.} and Alix Trouillet and Krey, {Jocelyn F.} and Peter Barr-Gillespie and Oghalai, {John S.} and Ulrich M{\"u}ller",
year = "2016",
month = "8",
day = "31",
doi = "10.1523/JNEUROSCI.0093-16.2016",
language = "English (US)",
volume = "36",
pages = "9201--9216",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "35",

}

TY - JOUR

T1 - Neuroplastin isoform Np55 is expressed in the stereocilia of outer hair cells and required for normal outer hair cell function

AU - Zeng, Wei Zheng

AU - Grillet, Nicolas

AU - Dewey, James B.

AU - Trouillet, Alix

AU - Krey, Jocelyn F.

AU - Barr-Gillespie, Peter

AU - Oghalai, John S.

AU - Müller, Ulrich

PY - 2016/8/31

Y1 - 2016/8/31

N2 - Neuroplastin (Nptn) is a member of the Ig superfamily and is expressed in two isoforms, Np55 and Np65. Np65 regulates synaptic transmission but the function of Np55 is unknown. In anN-ethyl-N-nitrosaurea mutagenesis screen, we have now generated a mouse line with an Nptn mutation that causes deafness. We show that Np55 is expressed in stereocilia of outer hair cells (OHCs) but not inner hair cells and affects interactions of stereocilia with the tectorial membrane. In vivo vibrometry demonstrates that cochlear amplification is absent in Nptn mutant mice, which is consistent with the failure of OHC stereocilia to maintain stable interactions with the tectorial membrane. Hair bundles show morphological defects as the mutant mice age and while mechanotransduction currents can be evoked in early postnatal hair cells, cochlea microphonics recordings indicate that mechanon transduction is affected as the mutant mice age. We thus conclude that differential splicing leads to functional diversification of Nptn, where Np55 is essential for OHC function, while Np65 is implicated in the regulation of synaptic function.

AB - Neuroplastin (Nptn) is a member of the Ig superfamily and is expressed in two isoforms, Np55 and Np65. Np65 regulates synaptic transmission but the function of Np55 is unknown. In anN-ethyl-N-nitrosaurea mutagenesis screen, we have now generated a mouse line with an Nptn mutation that causes deafness. We show that Np55 is expressed in stereocilia of outer hair cells (OHCs) but not inner hair cells and affects interactions of stereocilia with the tectorial membrane. In vivo vibrometry demonstrates that cochlear amplification is absent in Nptn mutant mice, which is consistent with the failure of OHC stereocilia to maintain stable interactions with the tectorial membrane. Hair bundles show morphological defects as the mutant mice age and while mechanotransduction currents can be evoked in early postnatal hair cells, cochlea microphonics recordings indicate that mechanon transduction is affected as the mutant mice age. We thus conclude that differential splicing leads to functional diversification of Nptn, where Np55 is essential for OHC function, while Np65 is implicated in the regulation of synaptic function.

KW - Amplification

KW - Deafness

KW - Hair cells

KW - Inner ear

KW - Neuroplastin

KW - Tectorial membrane

UR - http://www.scopus.com/inward/record.url?scp=84984979182&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84984979182&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0093-16.2016

DO - 10.1523/JNEUROSCI.0093-16.2016

M3 - Article

VL - 36

SP - 9201

EP - 9216

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 35

ER -