The actin-binding proteins eps8 and gelsolin have complementary roles in regulating the growth and stability of mechanosensory hair bundles of mammalian cochlear outer hair cells.
Sound transduction depends upon mechanosensitive channels localized on the hair-like bundles that project from the apical surface of cochlear hair cells. Hair bundles show a stair-case structure composed of rows of stereocilia, and each stereocilium contains a core of tightly-packed and uniformly-polarized actin filaments. The growth and maintenance of the stereociliary actin core are dynamically regulated. Recently, it was shown that the actin-binding protein gelsolin is expressed in the stereocilia of outer hair cells (OHCs) and in its absence they become long and straggly. Gelsolin is part of a whirlin scaffolding protein complex at the stereocilia tip, which has been shown to interact with other actin regulatory molecules such as Eps8. Here we investigated the physiological effects associated with the absence of gelsolin and its possible overlapping role with Eps8. We found that, in contrast to Eps8, gelsolin does not affect mechanoelectrical transduction during immature stages of development. Moreover, OHCs from gelsolin knockout mice were able to mature into fully functional sensory receptors as judged by the normal resting membrane potential and basolateral membrane currents. Mechanoelectrical transducer current in gelsolin-Eps8 double knockout mice showed a profile similar to that observed in the single mutants for Eps8. We propose that gelsolin has a non-overlapping role with Eps8. While Eps8 is mainly involved in the initial growth of stereocilia in both inner hair cells (IHCs) and OHCs, gelsolin is required for the maintenance of mature hair bundles of low-frequency OHCs after the onset of hearing.
Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
Jennifer
J
Olt
Medical Research Council (MRC), Mammalian Genetics Unit, Harwell, United Kingdom.
Philomena
P
Mburu
Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
Stuart L
SL
Johnson
Medical Research Council (MRC), Mammalian Genetics Unit, Harwell, United Kingdom.
Andy
A
Parker
Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
Stephanie
S
Kuhn
Medical Research Council (MRC), Mammalian Genetics Unit, Harwell, United Kingdom.
Mike
M
Bowl
Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
Walter
W
Marcotti
Medical Research Council (MRC), Mammalian Genetics Unit, Harwell, United Kingdom.
Steve D M
SD
Brown
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism*; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008465:Mechanoreceptors / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds
C513734:Abi1 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C073804:FM1 43; D018260:Gelsolin; D008840:Microfilament Proteins; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds