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.
Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Moritoshi
M
Hirono
Charlotte S
CS
Denis
Guy P
GP
Richardson
Peter G
PG
Gillespie
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