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: We then investigated whether the absence of plastin 1 affected the adaptation properties of the MET current by stimulating the hair bundles of OHCs by mechanical step stimuli instead of sinusoids. In both het and Pls1 KO OHCs, excitatory bundle movements with non-saturating stimuli elicited rapid inward currents at a holding potential of –81 mV that declined or adapted over time (Fig. 9A and B, arrows). Inhibitory hair bundle stimulation shut off the small fraction of the current flowing at rest, and the offset of large inhibitory steps caused a transient rebound (downward current dip: Fig. 9A and B, arrowheads). All these manifestations of MET current adaptation were absent when stepping the membrane potential to +99 mV (Fig. 9C and D), which prevents or strongly reduces Ca2+ entry into the MET channels. This is consistent with Ca2+ entry driving adaptation as previously demonstrated in hair cells from lower vertebrates (29,31), but somehow different from recent findings in rat OHCs (32). At −81 mV, the onset adaptation for excitatory stimuli was best fitted with two time constants (τfast and τslow) in both het and Pls1 KO OHCs (Fig. 9A and B, arrows) with τfast (Fig. 9E, left panel), but not τslow (Fig. 9E, right panel), being significantly faster in het than in Pls1 KO OHCs (P < 0.05). The extent of adaptation for non-saturating excitatory stimuli (Fig. 9A and B) was also significantly increased (P < 0.0001) in Pls1 KO compared with het OHCs (Fig. 9F). Although these data were collected on pre-hearing OHCs only, they indicate that plastin 1 is dispensable for mechanotransduction. However, the subtle but significant slowing of the fast adaptation, but overall increase in its extent, to mechanical stimuli suggests that even in the absence of any visible morphological defect, some of the functional properties of stereocilia differ in plastin 1 deficient hair cells.Figure 9.
Affiliation: Centre for Auditory Research, UCL Ear Institute, University College London, London, UK.