Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins.
Nature's fastest motors are the cochlear outer hair cells (OHCs). These sensory cells use a membrane protein, Slc26a5 (prestin), to generate mechanical force at high frequencies, which is essential for explaining the exquisite hearing sensitivity of mammalian ears. Previous studies suggest that...
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2015-09-01
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doaj-ae9f8a167b014b09ac6113b4a1b70ee82020-11-24T21:56:17ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-09-01119e100550010.1371/journal.pgen.1005500Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins.Tetsuji YamashitaPierre HakizimanaSiva WuAhmed HassanStefan JacobJamshid TemirovJie FangMarcia Mellado-LagardeRichard GurskyLinda HornerBarbara LeibigerSara LeijonVictoria E CentonzePer-Olof BerggrenSharon FraseManfred AuerWilliam E BrownellAnders FridbergerJian ZuoNature's fastest motors are the cochlear outer hair cells (OHCs). These sensory cells use a membrane protein, Slc26a5 (prestin), to generate mechanical force at high frequencies, which is essential for explaining the exquisite hearing sensitivity of mammalian ears. Previous studies suggest that Slc26a5 continuously diffuses within the membrane, but how can a freely moving motor protein effectively convey forces critical for hearing? To provide direct evidence in OHCs for freely moving Slc26a5 molecules, we created a knockin mouse where Slc26a5 is fused with YFP. These mice and four other strains expressing fluorescently labeled membrane proteins were used to examine their lateral diffusion in the OHC lateral wall. All five proteins showed minimal diffusion, but did move after pharmacological disruption of membrane-associated structures with a cholesterol-depleting agent and salicylate. Thus, our results demonstrate that OHC lateral wall structure constrains the mobility of plasma membrane proteins and that the integrity of such membrane-associated structures are critical for Slc26a5's active and structural roles. The structural constraint of membrane proteins may exemplify convergent evolution of cellular motors across species. Our findings also suggest a possible mechanism for disorders of cholesterol metabolism with hearing loss such as Niemann-Pick Type C diseases.http://europepmc.org/articles/PMC4564264?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tetsuji Yamashita Pierre Hakizimana Siva Wu Ahmed Hassan Stefan Jacob Jamshid Temirov Jie Fang Marcia Mellado-Lagarde Richard Gursky Linda Horner Barbara Leibiger Sara Leijon Victoria E Centonze Per-Olof Berggren Sharon Frase Manfred Auer William E Brownell Anders Fridberger Jian Zuo |
spellingShingle |
Tetsuji Yamashita Pierre Hakizimana Siva Wu Ahmed Hassan Stefan Jacob Jamshid Temirov Jie Fang Marcia Mellado-Lagarde Richard Gursky Linda Horner Barbara Leibiger Sara Leijon Victoria E Centonze Per-Olof Berggren Sharon Frase Manfred Auer William E Brownell Anders Fridberger Jian Zuo Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. PLoS Genetics |
author_facet |
Tetsuji Yamashita Pierre Hakizimana Siva Wu Ahmed Hassan Stefan Jacob Jamshid Temirov Jie Fang Marcia Mellado-Lagarde Richard Gursky Linda Horner Barbara Leibiger Sara Leijon Victoria E Centonze Per-Olof Berggren Sharon Frase Manfred Auer William E Brownell Anders Fridberger Jian Zuo |
author_sort |
Tetsuji Yamashita |
title |
Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. |
title_short |
Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. |
title_full |
Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. |
title_fullStr |
Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. |
title_full_unstemmed |
Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. |
title_sort |
outer hair cell lateral wall structure constrains the mobility of plasma membrane proteins. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2015-09-01 |
description |
Nature's fastest motors are the cochlear outer hair cells (OHCs). These sensory cells use a membrane protein, Slc26a5 (prestin), to generate mechanical force at high frequencies, which is essential for explaining the exquisite hearing sensitivity of mammalian ears. Previous studies suggest that Slc26a5 continuously diffuses within the membrane, but how can a freely moving motor protein effectively convey forces critical for hearing? To provide direct evidence in OHCs for freely moving Slc26a5 molecules, we created a knockin mouse where Slc26a5 is fused with YFP. These mice and four other strains expressing fluorescently labeled membrane proteins were used to examine their lateral diffusion in the OHC lateral wall. All five proteins showed minimal diffusion, but did move after pharmacological disruption of membrane-associated structures with a cholesterol-depleting agent and salicylate. Thus, our results demonstrate that OHC lateral wall structure constrains the mobility of plasma membrane proteins and that the integrity of such membrane-associated structures are critical for Slc26a5's active and structural roles. The structural constraint of membrane proteins may exemplify convergent evolution of cellular motors across species. Our findings also suggest a possible mechanism for disorders of cholesterol metabolism with hearing loss such as Niemann-Pick Type C diseases. |
url |
http://europepmc.org/articles/PMC4564264?pdf=render |
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