Year: 2015
Type: article
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.
Source: PLoS Genetics
Authors: 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
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: Wenner-Gren Foundation, National Organization for Hearing Research Foundation, Northwestern University, St. Jude Children's Research Hospital, Wellcome Trust, Stiftelsen Tysta Skolan, American Lebanese Syrian Associated Charities, Vetenskapsrådet, National Institutes of Health, Medical Research Council, Office of Naval Research, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of General Medical Sciences
Awards: G1281772883, Genetic analysis of mammalian hearing sensitivity, G1871602402, G2474954790, G2649222700, MODULATION RESPONSE IN THE INFERIOR COLLICULUS, G3528049099, Electromechanics of the Cochlear Outer Hair Cell, G393976499, Electron Microscopy of Biological Macromolecules, G4856111422, G5383298809, G5998785214, Drug discovery for hair cell regeneration in adult mammalian cochleae, Intracochlear Electrochemical Gradients, G8281456828, Cancer Center Support Grant (CCSG)
OpenAlex ID: W2158936031