The organization of the molecular force sensor in cochlear hair cells.
We have examined the role of transmembrane channel-like protein, TMC1, as the central component of the hair cell mechanotransducer (MET) channel by characterizing transduction in mice harboring mutations in the putative pore region, TM domains 4-7. Two mutations (Tmc1 p.D528N or Tmc1 p.E520Q) decreased channel conductance and two (Tmc1 p. D569N or Tmc1 p.W554L) lowered expression. All Tmc1 mutations reduced Ca2+ influx into the hair bundle. These mutations ultimately led to hair cell apoptosis and deafness by four weeks post-natal and corroborate TMC1 as the MET channel pore. The channel complex also contains the accessory subunit, LHFPL5. In Lhfpl5 knockout mice, MET currents could still be activated by hair bundle deflections but were reduced in amplitude and sensitivity. The working range and half-saturation of the MET current were increased and gating stiffness virtually abolished, suggesting LHFPL5 is part of the mechanical coupling between the tip-link PCDH15 and TMC1.
Date: 6 October 2023, 11:00 (Friday, 0th week, Michaelmas 2023)
Venue: Sherrington Library, off Parks Road OX1 3PT
Speakers: Speaker to be announced
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organiser: Prof Andrew King (University of Oxford)
Host: Prof Andrew King (University of Oxford)
Part of: Neuroscience Theme Guest Speakers (DPAG)
Booking required?: Not required
Audience: Members of the University only
Editor: Peter Belk