Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice.
Bottom Line: Auditory hair cells developed normally in Pls1 KO, but in young adult animals, the stereocilia of inner hair cells were reduced in width and length.These results show that in contrast to other actin-bundling proteins such as espin, harmonin or Eps8, plastin 1 is dispensable for the initial formation of stereocilia.Hence, mutations in the human PLS1 gene may be associated with relatively mild and progressive forms of hearing loss.
Affiliation: Centre for Auditory Research, UCL Ear Institute, University College London, London, UK.Show MeSH
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Mentions: Besides its role in maintaining the morphology and structure of adult hair cell stereocilia, plastin 1 may be important for mechanoelectrical transduction. To test this, mechanoelectrical transducer (MET) currents were recorded from P5–P8 apical-coil OHCs by displacing their hair bundles in the excitatory and inhibitory direction using a piezo-driven fluid-jet (26,27). The apparent overall steady-state stiffness of the hair bundle measured in het OHCs (6.3 ± 0.6 mN/m, n = 16) was similar to that of Pls1 KO cells (8.3 ± 1.0 mN/m, n = 11) and comparable with that measured from wild-type mouse OHCs in organotypic cultures (28). Upon moving the bundles towards the taller stereocilia (i.e. in the excitatory direction) and at negative membrane potentials, a large inward MET current could be elicited in OHCs from both het and Pls1 KO mice (Fig. 8A and B). The maximum MET current was found to be similar between het (−937 ± 46 pA at −81 mV, n = 7) and KO cells (−843 ± 34 pA at −81 mV, n = 12). Any resting current flowing through open MET channels in the absence of mechanical stimulation was reduced when bundles were moved towards the shorter stereocilia (i.e. in the inhibitory direction) in all het and Pls1 KO OHCs (Fig. 8A and B, arrows). Because the MET current reverses near 0 mV, it became outward when excitatory bundle stimulation was applied during voltage steps positive to its reversal potential (Fig. 8A–C). At positive potentials, the larger resting transducer current (e.g. at +99 mV in Fig. 8A and B: arrows) is due to an increased open probability of the transducer channel resulting from a reduced driving force for Ca2+ influx (29,30). The above-mentioned results indicate that the biophysical properties of the transducer channel, including the presence of a resting current, are not affected by the absence of plastin 1.Figure 8.
Affiliation: Centre for Auditory Research, UCL Ear Institute, University College London, London, UK.