PETER GORDON GILLESPIE

..Introduction of Y61G myosin-Ibeta molecules into a cell should permit selective inhibition by N(6)-modified ADP analogs of cellular processes dependent on myosin-Ibeta...

..Although these are excellent candidates for the three components, definitive experiments supporting each identification have yet to be performed...

..The sliding-filament hypothesis for muscle contraction has thus led to a detailed understanding of the behaviour of hair cells...

..This review focuses on the detailed operation of the adaptation motor and the functional consequences of the incorporation of this specific myosin isozyme into the motor complex...

..How calmodulin binds to these IQ domains is the subject of this report...

..Despite their faults, we believe that the names adopted by the HUGO nomenclature group for genome annotation are the best compromise, and we recommend universal adoption...

..But recent progress in both invertebrates and vertebrates is beginning to reveal the identities of proteins essential for transduction...

..The calcium-sensitive binding of calmodulin to myosin-1c may therefore modulate the interaction of the adaptation motor with other components of the transduction apparatus...

..We instead propose a 'cochlear transformer' mechanism to interpret cochlear performance...

..quot;Fast adaptation," the rapid closure of transduction channels following a mechanical stimulus, appears to be intimately involved in bundle-based amplification...

..Myo1c therefore remains the myosin isozyme best localized to carry out transducer adaptation...

..PIP(2) depletion also causes a loss in transduction current. PIP(2) therefore plays an essential role in hair cell adaptation and transduction...

..Consistent with this critical role in hair bundle function, the creatine kinase circuit is essential for high-sensitivity hearing as demonstrated by hearing loss in creatine kinase knockout mice...

..At present, we are forced to speculate as to the transduction channel's identity; functional characteristics suggest, however, that it may well belong to transient receptor potential superfamily of ion channels...

..This result suggests that although TRPN1 is unlikely to be the transduction channel of stereocilia, it plays an essential role, functionally related to transduction, in the kinocilium...

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..This mechanism allows the hair cell to remove H+ generated by Ca2+ pumping without ATP hydrolysis in the cell...

..These results indicate that PS exposure on the external leaflet, presumably requiring vesicular transport, results from elevation of intracellular cAMP, which can be triggered by Na(+) entry into hair cells...

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..Because ahl8 accelerates hearing loss only in the presence of mutant cadherin 23, a component of hair-cell tip links, mechanotransduction and actin crosslinking must be functionally interrelated...

..This project is an essential first step in understanding what makes up a hair bundle. ..

..The complex of proteins in hair cells that transduce sound are still largely unknown; the goal of this project is to identify and characterize them, as they are essential for hearing. ..

..The complex of proteins in hair cells that transduce sound are still largely unknown; the goal of this project is to identify and characterize them, as they are essential for hearing. ..

..Together, the experiments in this proposal will allow us to determine how lipids regulate transduction and adaptation. ..

..Together, the experiments in this proposal will allow us to determine how lipids regulate transduction and adaptation. ..

..The complex of proteins in hair cells that transduce sound are still largely unknown; the goal of this project is to identify and characterize them, as they are essential for hearing. ..

..The complex of proteins in hair cells that transduce sound are still largely unknown;the goal of this project is to identify and characterize them, as they are essential for hearing. ..

..4) Finally, a combination of approaches will be applied to further characterize and eventually identify the elusive transduction channel. ..

..We expect that these dynamics experiments with FRAP will tie together properties of myosin isozymes and their binding proteins, both at steady-state and during tip-link regeneration. ..

..These experiments will allow us to identify the major proteins of the bundle and allow us to focus on proteins functionally important for bundle function. ..

..If re-expression of PMCA2 in hair cells rescues auditory function in these otherwise PMCA2-deficient mice, the key location of PMCA2 in the ear must be the hair cell. ..

..More significantly, these experiments will allow us to design rational approaches to detecting and ameliorating hearing loss and disrupted balance. ..