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Tension-dependent RHGF-1 recruitment to stress fibers drives robust spermathecal tissue contraction

  • Shiri Avivi Kela
  • , Kriti Sethi
  • , Pei Yi Tan
  • , Danesha Suresh
  • , Hui Ting Ong
  • , Perla G. Castaneda
  • , Mustafi R. Amin
  • , Tal Laviv
  • , Erin J. Cram
  • , Jan Faix
  • , Ronen Zaidel-Bar
  • National University of Singapore
  • Northeastern University
  • Hannover Medical School

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Contractile epithelial tubes are found in various organs, such as lung airways and blood capillaries. Their ability to sense luminal pressure and respond with adequate contractility is essential for their physiology, and its mis-regulation results in diseases such as asthma and hypertension. Here, we describe a mechanoresponsive regulatory pathway downstream of tissue stretching that controls contraction of the C. elegans spermatheca, a tubular structure where fertilization occurs. Using live-imaging, we show that ovulation-induced stretching of spermathecal cells leads to recruitment of the RhoGEF RHGF-1 to stress fibers, which activates RHO-1 and myosin II in a positive feedback loop. Through deletion analysis, we identified the PDZ domain of RHGF-1 as responsible for F-actin binding, and genetic epistasis analysis with the RhoGAP spv-1 demonstrated that tension-dependent recruitment of RHGF-1 to F-actin is required for robust spermathecal contractility. Our study illustrates how mechanosensitive regulators of Rho GTPases provide epithelial tubes the ability to tune their contractility in response to internal pressure.

Original languageEnglish
Article numbere202203105
JournalJournal of Cell Biology
Volume222
Issue number2
DOIs
StatePublished - 6 Feb 2023

Funding

FundersFunder number
Joan and Jaime Constantiner Institute for Molecular Genetics
United States - Israel Binational Science Foundation2017657
National Science Foundation1816640
Deutsche ForschungsgemeinschaftFa330/12-3
Israel Science Foundation1293/17, 767/20
National Institutes of HealthP40 OD010440

    UN SDGs

    This output contributes to the following UN Sustainable Development Goals (SDGs)

    1. SDG 3 - Good Health and Well-being
      SDG 3 Good Health and Well-being

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