Tuning of the outer hair cell motor by membrane cholesterol.
Cholesterol affects diverse biological processes, in many cases by modulating the function of integral membrane proteins. We observed that alterations of cochlear cholesterol modulate hearing in mice. Mammalian hearing is powered by outer hair cell (OHC) electromotility, a membrane-based motor mechanism that resides in the OHC lateral wall. We show that membrane cholesterol decreases during maturation of OHCs. To study the effects of cholesterol on hearing at the molecular level, we altered cholesterol levels in the OHC wall, which contains the membrane protein prestin. We show a dynamic and reversible relationship between membrane cholesterol levels and voltage dependence of prestin-associated charge movement in both OHCs and prestin-transfected HEK 293 cells. Cholesterol levels also modulate the distribution of prestin within plasma membrane microdomains and affect prestin self-association in HEK 293 cells. These findings indicate that alterations in membrane cholesterol affect prestin function and functionally tune the outer hair cell.
Rajagopalan
Lavanya
L
Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery, Huffington Center on Aging and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Greeson
Jennifer N
JN
Xia
Anping
A
Liu
Haiying
H
Sturm
Angela
A
Raphael
Robert M
RM
Davidson
Amy L
AL
Oghalai
John S
JS
Pereira
Fred A
FA
Brownell
William E
WE
D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000378:metabolism*; D006309:Hearing / Q000502:physiology*; D006801:Humans; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D000076988:Sulfate Transporters; D014162:Transfection
D027321:Anion Transport Proteins; D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; C498719:SLC26A5 protein, human; D000076988:Sulfate Transporters; D002784:Cholesterol