TY - JOUR
T1 - Pivotal role of actin depolymerization in the regulation of cochlear outer hair cell motility
AU - Matsumoto, Nozomu
AU - Kitani, Rei
AU - Maricle, Anastasiya
AU - Mueller, Melissa
AU - Kalinec, Federico
N1 - Funding Information:
This work was supported by National Institutes of Health grant No. DC010146 and House Ear Institute. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the House Ear Institute.
PY - 2010/10/6
Y1 - 2010/10/6
N2 - Cochlear outer hair cells undergo reversible changes in shape when externally stimulated. This response, known as OHC motility, is a central component of the cochlear amplifier, the mechanism responsible for the high sensitivity of mammalian hearing. We report that actin depolymerization, as regulated by activation/inhibition of LIMK/cofilin-mediated pathways, has a pivotal role in OHC motility. LIMK-mediated cofilin phosphorylation, which inhibits the actin depolymerizing activity of this protein, increases both electromotile amplitude and total length of guinea pig OHCs. In contrast, a decrease in cofilin phosphor- ylation reduces both OHC electromotile amplitude and OHC length. Experiments with acetylcholine and lysophosphatidic acid indicate that the effects of these agents on OHC motility are associated with regulation of cofilin phosphorylation via different signaling cascades. On the other hand, nonlinear capacitance measurements confirmed that all observed changes in OHC motile response were independent of the performance of the motor protein prestin. Altogether, these results strongly support the hypothesis that the cytoskeleton has a major role in the regulation of OHC motility, and identify actin depolymerization as a key process for modulating cochlear amplification.
AB - Cochlear outer hair cells undergo reversible changes in shape when externally stimulated. This response, known as OHC motility, is a central component of the cochlear amplifier, the mechanism responsible for the high sensitivity of mammalian hearing. We report that actin depolymerization, as regulated by activation/inhibition of LIMK/cofilin-mediated pathways, has a pivotal role in OHC motility. LIMK-mediated cofilin phosphorylation, which inhibits the actin depolymerizing activity of this protein, increases both electromotile amplitude and total length of guinea pig OHCs. In contrast, a decrease in cofilin phosphor- ylation reduces both OHC electromotile amplitude and OHC length. Experiments with acetylcholine and lysophosphatidic acid indicate that the effects of these agents on OHC motility are associated with regulation of cofilin phosphorylation via different signaling cascades. On the other hand, nonlinear capacitance measurements confirmed that all observed changes in OHC motile response were independent of the performance of the motor protein prestin. Altogether, these results strongly support the hypothesis that the cytoskeleton has a major role in the regulation of OHC motility, and identify actin depolymerization as a key process for modulating cochlear amplification.
UR - http://www.scopus.com/inward/record.url?scp=77958506267&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77958506267&partnerID=8YFLogxK
U2 - 10.1016/j.bpj.2010.08.015
DO - 10.1016/j.bpj.2010.08.015
M3 - Article
C2 - 20923640
AN - SCOPUS:77958506267
SN - 0006-3495
VL - 99
SP - 2067
EP - 2076
JO - Biophysical Journal
JF - Biophysical Journal
IS - 7
ER -