The smooth muscle titin filament system regulates uterus contractility and implantation

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.

Disease-associated MYH11 tail variants disrupt vascular smooth muscle myosin II filament dynamics and cell mechanics
S. K. Demeulenaere, M. A. Bennett, H. Patel +4
bioRxiv22 Oct 2026PreprintCC BY-NC-NDFull textCell biologybioRxiv
The single-PDZ domain protein TXBP-3 regulates contractility in the C. elegans spermatheca
M. Khalid, E. J. Cram
bioRxiv5 Oct 2026PreprintCC BY-NCFull textCell biologybioRxiv
Dynamic Filament Assembly Regulates the Prolyl Aminopeptidase Activity of Plant Immune Protein DM3
N. Kim, W.-L. Wan, Y. Y. Tan +3
bioRxiv3 Sep 2026PreprintPublic domainFull textPlant biologybioRxiv
Rhinovirus C15 Attenuates Relaxation and cAMP Production in Human Airways and Smooth Muscle
E. B. Gebski, V. Parikh, H. Lam +8
American Journal of Respiratory Cell and Molecular Biology9 Oct 2026Peer-reviewedLicence not statedFull text9 citedMicrobiologyHAL
Rhinovirus C15 Induces Airway Hyperresponsiveness via Calcium Mobilization in Airway Smooth Muscle
V. Parikh, J. Scala, R. Patel +8
American Journal of Respiratory Cell and Molecular Biology9 Oct 2026Peer-reviewedLicence not stated23 citedMicrobiologyHAL

Cite

BibTeX RIS

BibTeX

@article{sur2026smooth,
  title = {{The smooth muscle titin filament system regulates uterus contractility and implantation}},
  author = {V Juhi Sur and Claudia Fink and Nora Bergmann and Rene Jüttner and Melissa Klingeberg and Fabian Coscia and Lorena Suarez-Artiles and Philipp Mertins and Johanna Elisabeth Fritsch and Melissa Birol and Maik Gollasch and Michael Gotthardt},
  journal = {iScience},
  year = {2026},
  month = oct,
  doi = {10.1016/j.isci.2026.117888},
  url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03271-2},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - The smooth muscle titin filament system regulates uterus contractility and implantation
AU  - V Juhi Sur
AU  - Claudia Fink
AU  - Nora Bergmann
AU  - Rene Jüttner
AU  - Melissa Klingeberg
AU  - Fabian Coscia
AU  - Lorena Suarez-Artiles
AU  - Philipp Mertins
AU  - Johanna Elisabeth Fritsch
AU  - Melissa Birol
AU  - Maik Gollasch
AU  - Michael Gotthardt
PY  - 2026
DA  - 2026/10/14
JO  - iScience
DO  - 10.1016/j.isci.2026.117888
UR  - https://www.cell.com/iscience/fulltext/S2589-0042(26)03271-2
AB  - 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.
SN  - 2589-0042
ER  -

Abstract

Related

Cite