Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 languageEnglish (US)
Article numbere1005500
JournalPLoS Genetics
Volume11
Issue number9
DOIs
StatePublished - Sep 9 2015
Externally publishedYes

Fingerprint

Outer Auditory Hair Cells
hair
membrane proteins
Cell Wall
blood proteins
hairs
Blood Proteins
Membrane Proteins
plasma membrane
Cell Membrane
membrane
plasma
hearing
protein
Hearing
Membranes
Type C Niemann-Pick Disease
Cholesterol
cells
Salicylates

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Yamashita, T., Hakizimana, P., Wu, S., Hassan, A., Jacob, S., Temirov, J., ... Zuo, J. (2015). Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. PLoS Genetics, 11(9), [e1005500]. https://doi.org/10.1371/journal.pgen.1005500

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 journalArticle

Yamashita, T, Hakizimana, P, Wu, S, Hassan, A, Jacob, S, Temirov, J, Fang, J, Mellado-Lagarde, M, Gursky, R, Horner, L, Leibiger, B, Leijon, S, Centonze, VE, Berggren, PO, Frase, S, Auer, M, Brownell, WE, Fridberger, A & Zuo, J 2015, 'Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins', PLoS Genetics, vol. 11, no. 9, e1005500. https://doi.org/10.1371/journal.pgen.1005500
Yamashita T, Hakizimana P, Wu S, Hassan A, Jacob S, Temirov J et al. Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. PLoS Genetics. 2015 Sep 9;11(9). e1005500. https://doi.org/10.1371/journal.pgen.1005500
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. / Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. In: PLoS Genetics. 2015 ; Vol. 11, No. 9.
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