Cnidarian mechanosensory cells as ancestors of vertebrate hair cells: Molecular targeting of an ancient mechanotransduction complex.

Authors

Zeeshan Z Banday, Amelia M Randich, Raymond E Hulse, Zhen Tong, Jamie A Havrilak, Tomas Osorno-Ferro, Emily Watto, Evgeniya A Demchenko, Zachary Fournier, Nicolas Grillet, Marcos Sotomayor, Michael J Layden, Jocelyn Malamy, Eduardo Perozo

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 40. Pages e2607106123. Oct 06, 2026. Epub Sep 28, 2026.

Abstract

Conversion of mechanical stimuli into electrical signals underlies many physiological processes, including auditory and vestibular functions. In vertebrate hair cells, the mechanoelectrical transduction complex (METC)-a multiprotein and Ca²⁺-dependent sound and motion receptor-is located at the stereociliary tips within the hair bundle. Transmembrane channel-like 1 and 2 (TMC1 and TMC2) proteins function as the mechanosensitive channels in this complex. To investigate the evolutionary origins of vertebrate hair cells we have evaluated whether cnidarian nematocytes are related to the vertebrate hair cells at the cellular and molecular levels. The hair-bundles of nematocytes resemble those found in vertebrate hair cells, including the presence of extracellular protein tethers. Cnidarian TMC5 and TMC7 localize to the hair bundles, the proposed site of MET channel activity. MET channel permeant FM dye uptake experiments demonstrate that mechanically activated nematocytes incorporate dye through their stereovillar bundle and not through the kinocilium-like cnidocil. RNAi-mediated knockdown of TMC5 and TMC7 significantly reduced nematocyte eversion in Clytia and Nematostella, pointing to their fundamental role in mechanotransduction. In contrast, similar experiments show that the TRP channel NompC is not required in this response. Overall, we present morphological, behavioral, pharmacological, bioinformatic, and reverse genetics data supporting an evolutionary relationship between the common ancestors of cnidarian nematocytes and vertebrate hair cells. Our findings highlight the conservation of mechanotransduction mechanisms based on TMC channels and offer evolutionary insights to the origin of mechanical signaling based on stereovillar bundle deflection.

PMID:
42804640
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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