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bioRxiv · 10.1101/2022.08.19.504503

Redefining the structure of tip-links in hair-cells

Kaur, V.·Ghosh, S. K.·Bhatia, T.·Rakshit, S.
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Abstract

Tip-link, the gating-spring in hearing, modulates the mechanoelectrotransduction process and protects the hearing sensory machineries from overexcited auditory inputs. Tip-links are formed by two exceptionally long cadherins, cadherin-23 and protocadherin-15. It is proposed that both the cadherins first independently form cis-dimers through lateral interactions and finally, engage in trans-interactions to form the heterotetrameric assembly in tip-links. In fact, the molecular details of the protocadherin cis-dimers are well-understood. However, little structural and molecular details are known for independent cis-dimer of cadherin-23. Using photo-induced cross-linking of unmodified proteins in solution and on lipid-membranes, we observed no trace of cadherin-23 cis-dimers, rather we captured trans-homodimers of cadherin-23. We thus, redefine the tip-link structure where protocadherin-15 remains as cis-dimers, however, two individual cadherin-23 binds to protocadherin-15 cis-dimer for tip linking.

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Kaur, V., Ghosh, S. K., Bhatia, T., Rakshit, S.. 2022-08-20. Redefining the structure of tip-links in hair-cells. https://doi.org/10.1101/2022.08.19.504503

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