Hair cells require phosphatidylinositol 4,5-bisphosphate for mechanical transduction and adaptation.
After opening in response to mechanical stimuli, hair cell transduction channels adapt with fast and slow mechanisms that each depend on Ca(2+). We demonstrate here that transduction and adaptation require phosphatidylinositol 4,5-bisphosphate (PIP(2)) for normal kinetics. PIP(2) has a striking distribution in hair cells, being excluded from the basal region of hair bundles and apical surfaces of frog saccular hair cells. Localization of a phosphatidylinositol lipid phosphatase, Ptprq, to these PIP(2)-free domains suggests that Ptprq maintains low PIP(2) levels there. Depletion of PIP(2) by inhibition of phosphatidylinositol 4-kinase or sequestration by aminoglycosides reduces the rates of fast and slow adaptation. PIP(2) and other anionic phospholipids bind directly to the IQ domains of myosin-1c, the motor that mediates slow adaptation, permitting a strong interaction with membranes and likely regulating the motor's activity. PIP(2) depletion also causes a loss in transduction current. PIP(2) therefore plays an essential role in hair cell adaptation and transduction.
Hirono
Moritoshi
M
Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Denis
Charlotte S
CS
Richardson
Guy P
GP
Gillespie
Peter G
PG
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D008854:Microscopy, Electron; D009218:Myosins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000187:drug effects / Q000378:metabolism; D011894:Rana pipiens
D004791:Enzyme Inhibitors; D019269:Phosphatidylinositol 4,5-Diphosphate; D017027:Protein Tyrosine Phosphatases; D009218:Myosins