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| Item Type: | Article |
|---|---|
| Title: | The smooth muscle titin filament system regulates uterus contractility and implantation |
| Creators: |
Sur, V Juhi  ORCID: https://orcid.org/0000-0002-9530-5928, Fink, Claudia, Bergmann, Nora, Jüttner, Rene ORCID: https://orcid.org/0000-0003-3565-0698, Klingeberg, Melissa ORCID: https://orcid.org/0009-0002-4778-2874, Coscia, Fabian ORCID: https://orcid.org/0000-0002-2244-5081, Suarez Artiles, Lorena ORCID: https://orcid.org/0000-0001-7991-5446, Mertins, Philipp ORCID: https://orcid.org/0000-0002-2245-528X, Fritsch, Johanna Elisabeth, Birol, Melissa ORCID: https://orcid.org/0000-0003-3397-8446, Gollasch, Maik ORCID: https://orcid.org/0000-0003-2797-1934 and Gotthardt, Michael ORCID: https://orcid.org/0000-0003-1788-3172
|
| Abstract: | Coordinated uterine peristalsis positions embryos for implantation, but the mechanotransduction pathways controlling uterine wave coordination are not well defined. We combined smooth-muscle-specific deletion of titin M-band exons 1 and 2 with vertical agarose gel electrophoresis, mass spectrometry, uterine ring myography, imaging, transcriptomics, spatial proteomics, and targeted immunoblotting. We show that the myometrium expresses smooth-muscle titin and low-abundance full-length titin including the M-band kinase region. Conditional M-band deletion increased oxytocin-evoked force and area-under-the-curve while reducing coordinated wall motion, yielding fewer as well as crowded/mislocalized implantation sites and heavier placentas. Proteomics and immunoblotting identified disruption of an NBR1/p62 autophagy hub with downstream remodeling of excitability, metabolism, and wall mechanics. Reduced telokin and MLCK levels are consistent with impaired relaxation and increased Ca2+-sensitization. Together, these findings establish the titin M-band as a mechanotransductive signaling hub regulating peri-implantation motility with potential clinical relevance for optimizing implantation after in vitro fertilization and preventing ectopic pregnancy. |
| Keywords: | Animals, Mice |
| Source: | iScience |
| ISSN: | 2589-0042 |
| Publisher: | Elsevier / Cell Press |
| Volume: | 29 |
| Number: | 11 |
| Page Range: | 117888 |
| Number of Pages: | 1 |
| Date: | 20 November 2026 |
| Official Publication: | https://doi.org/10.1016/j.isci.2026.117888 |
| Related to: |
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