{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:56:34Z","timestamp":1790873794164,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,28]]},"group-title":"Cell Biology","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01HD118160"],"award-info":[{"award-number":["R01HD118160"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Spermiogenesis, the transformation of round spermatids into streamlined, fertilization-competent sperm, represents cellular morphogenesis at its most extreme\n                  <jats:sup>1,2<\/jats:sup>\n                  . Despite decades of effort, spermiogenesis remains difficult to recapitulate outside the testis\n                  <jats:sup>2,3<\/jats:sup>\n                  , highlighting the importance of cues within the native tissue environment. The nature of these cues, however, remains poorly understood. Here, we discover that mechanical stimulation elicits Ca\n                  <jats:sup>2+<\/jats:sup>\n                  entry in spermatids and identify transmembrane channel-like protein 5 (TMC5) as a principal mediator of this response. In both mouse and human testes, TMC5 is selectively expressed in spermatids and localized to the plasma membrane. TMC5 associates with TMC7 and calcium- and integrin-binding (CIB) proteins, mirroring TMC\u2013CIB mechanotransduction complexes in sensory organs\n                  <jats:sup>4,5<\/jats:sup>\n                  . Mechanistically, loss of\n                  <jats:italic>Tmc5<\/jats:italic>\n                  blocks mechanically evoked Ca\n                  <jats:sup>2+<\/jats:sup>\n                  entry, leading to disruptions in cytoskeletal remodeling and failure of CREM\u03c4-dependent transcriptional programs required for spermiogenesis\n                  <jats:sup>6<\/jats:sup>\n                  . Thus, TMC5 is required to couple mechanical cues to sperm development, with direct implications for male infertility.\n                <\/jats:p>","DOI":"10.64898\/2026.09.26.754653","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:00:23Z","timestamp":1790607623000},"source":"Crossref","is-referenced-by-count":0,"title":["Sperm development requires TMC5-dependent mechanoresponsive calcium entry"],"prefix":"10.64898","author":[{"given":"W.","family":"Sharon Zheng","sequence":"first","affiliation":[{"name":"Center for Membrane and Cell Physiology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"},{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Roa-De-La-Cruz","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Slocomb","sequence":"additional","affiliation":[{"name":"Center for Membrane and Cell Physiology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"},{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betta","family":"Chopard","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Cell Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelina","family":"Kierzek","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Lin","sequence":"additional","affiliation":[{"name":"Center for Membrane and Cell Physiology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"},{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Webb","sequence":"additional","affiliation":[{"name":"Center for Membrane and Cell Physiology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"},{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Jeffery","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia M.","family":"Santi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Bum","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer S.","family":"Bajikar","sequence":"additional","affiliation":[{"name":"Depertment of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Shenynkman","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bimal N.","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Hermann","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Geyer","sequence":"additional","affiliation":[{"name":"Department of 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