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

J Cell Biol. 2023 Feb 6;222(2):e202203105. doi: 10.1083/jcb.202203105. Epub 2022 Dec 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / metabolism
  • Female
  • GTPase-Activating Proteins / metabolism
  • Guanine Nucleotide Exchange Factors / metabolism
  • Muscle Contraction
  • Stress Fibers / metabolism
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Actins
  • RHGF-1 protein, C elegans
  • Guanine Nucleotide Exchange Factors
  • RHO-1 protein, C elegans
  • rho GTP-Binding Proteins
  • SPV-1 protein, C elegans
  • GTPase-Activating Proteins