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 journalArticlepeer-review

12 Scopus citations

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

ASJC Scopus subject areas

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

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