TY - JOUR
T1 - Tension-dependent RHGF-1 recruitment to stress fibers drives robust spermathecal tissue contraction
AU - Avivi Kela, Shiri
AU - Sethi, Kriti
AU - Tan, Pei Yi
AU - Suresh, Danesha
AU - Ong, Hui Ting
AU - Castaneda, Perla G.
AU - Amin, Mustafi R.
AU - Laviv, Tal
AU - Cram, Erin J.
AU - Faix, Jan
AU - Zaidel-Bar, Ronen
N1 - Publisher Copyright: © 2022 Kela et al.
PY - 2023/2/6
Y1 - 2023/2/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85144636748&partnerID=8YFLogxK
U2 - https://doi.org/10.1083/jcb.202203105
DO - https://doi.org/10.1083/jcb.202203105
M3 - مقالة
C2 - 36574264
SN - 0021-9525
VL - 222
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
M1 - e202203105
ER -