Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins.
2015 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 9, e1005500Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Public Library of Science , 2015. Vol. 11, no 9, e1005500
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-121278DOI: 10.1371/journal.pgen.1005500ISI: 000362203600001PubMedID: 26352669OAI: oai:DiVA.org:liu-121278DiVA: diva2:853036
Funding text: National Institutes of Health [DC006471, P30CA21765, DC00354, DC02775, P01GM051487]; Office of Naval Research [N000140911014, N000141210191, N000141210775]; Swedish Research Council [K2014-63X-14061-14-5]; Research Council for Working Life and Social Rese2015-09-112015-09-112016-03-24