Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | e1005500 |
| Journal | PLoS Genetics |
| Volume | 11 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 9 2015 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Ecology, Evolution, Behavior and Systematics
- Cancer Research
- Genetics(clinical)
Cite this
Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. / Yamashita, Tetsuji; Hakizimana, Pierre; Wu, Siva; Hassan, Ahmed; Jacob, Stefan; Temirov, Jamshid; Fang, Jie; Mellado-Lagarde, Marcia; Gursky, Richard; Horner, Linda; Leibiger, Barbara; Leijon, Sara; Centonze, Victoria E.; Berggren, Per Olof; Frase, Sharon; Auer, Manfred; Brownell, William E.; Fridberger, Anders; Zuo, Jian.
In: PLoS Genetics, Vol. 11, No. 9, e1005500, 09.09.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins
AU - Yamashita, Tetsuji
AU - Hakizimana, Pierre
AU - Wu, Siva
AU - Hassan, Ahmed
AU - Jacob, Stefan
AU - Temirov, Jamshid
AU - Fang, Jie
AU - Mellado-Lagarde, Marcia
AU - Gursky, Richard
AU - Horner, Linda
AU - Leibiger, Barbara
AU - Leijon, Sara
AU - Centonze, Victoria E.
AU - Berggren, Per Olof
AU - Frase, Sharon
AU - Auer, Manfred
AU - Brownell, William E.
AU - Fridberger, Anders
AU - Zuo, Jian
PY - 2015/9/9
Y1 - 2015/9/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84955569436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955569436&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1005500
DO - 10.1371/journal.pgen.1005500
M3 - Article
C2 - 26284659
AN - SCOPUS:84955569436
VL - 11
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 9
M1 - e1005500
ER -