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Details on Person The mechanoelectrical transduction (MET) channels (also call...
| Class:Id | Summation:9664674 |
|---|---|
| _displayName | The mechanoelectrical transduction (MET) channels (also call... |
| _timestamp | 2020-08-22 06:20:29 |
| created | [InstanceEdit:9664672] May, Bruce, 2019-10-26 |
| modified | [InstanceEdit:9664755] May, Bruce, 2019-10-27 [InstanceEdit:9665090] May, Bruce, 2019-10-29 [InstanceEdit:9667747] May, Bruce, 2019-11-16 [InstanceEdit:9668878] May, Bruce, 2019-11-30 [InstanceEdit:9690945] May, Bruce, 2020-06-07 [InstanceEdit:9698113] May, Bruce, 2020-08-22 |
| text | The mechanoelectrical transduction (MET) channels (also called mechanotransducer channels) located at the tips of stereocilia on the apical surface of inner hair cells (IHCs) are opened by mechanical force exerted on the channels by Cdh23:Pcdh15 tip links that connect the apex of the shorter stereocilium with the side of the taller stereocilium (Siemens et al. 2004, Ahmed et al. 2006, Kazmierczak et al. 2007, Narui and Sotomayor 2018, Oroz et al. 2019). A Cdh23 dimer is connected to the cytoskeleton of a taller stereocilium via Ush1c (Harmonin), Ush1g (Sans), and Myo7a (MyoVIIa) (Boeda et al. 2002, Adato et al. 2005, Bahloul et al. 2010, Grati and Kachar 2011, Bahloul et al. 2017). By a calcium-dependent interaction, a Cdh23 dimer on the side of a taller stereocilium is bound to a Pcdh15 dimer (Elledge et al. 2010, Schwander et al. 2009, Sotomayor et al. 2010) on the apex of a shorter stereocilium that interacts, possibly via Lhfpl5, with a MET channel on the shorter stereocilium (Mahendrasingam and Furness 2019). The MET complex contains at least Tmc1, Tmc2 (Kawashima et al. 2011, Pan et al. 2013, Beurg et al. 2015, Kurima et al. 2015, Corns et al. 2016, Beurg et al. 2018, Pan et al. 2018, Beurg et al. 2019, Goldring et al. 2019), Tmie (Zhao et al. 2014), Cib2 (Michel et al. 2017, Wang et al. 2017) and Lhfpl5 (also called Tmhs), which interacts with Pcdh15 (Xiong et al. 2012, Geng et al. 2013, Beurg et al. 2015, Ge et al. 2018). The actual pore-forming units of the complex have not yet been identified with certainty. In mice, Tmc2 expression is highest during the first week after birth and decreases in adulthood; Tmc1 expression is low in the first week after birth and increases in adulthood (Kawashima et al. 2011, Kurima et al. 2015). The MET channel may also contain additional, unidentified proteins (Beurg et al. 2014). Deflection of the stereocilia by sound causes increased tension on Cdh23:Pcdh15, resulting in an increased probability of the open state of the MET channel (Beurg et al. 2006, Pan et al. 2013, Beurg et al. 2018, Pan et al. 2018). The MET channel is relatively non-specific for cations (inferred from rat homologs) and allows calcium ions (Kim and Fettiplace 2013, Pan et al. 2013, Beurg et al. 2015, Corns et al. 2016, Corns et al. 2017) and potassium ions to pass from the extracellular scala media to the cytosol of the IHC. The resulting depolarization of the cell eventually results in glutamate-mediated activation of myelinated afferent neurons of the cochlear nerve. |
| (summation) | [Reaction:9659536] MET channel transports cations from the extracellular region into the cytosol of stereocilia of cochlear inner hair cell [Mus musculus] |
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