Stretch-induced actomyosin contraction in epithelial tubes: Mechanotransduction pathways for tubular homeostasis

Sethi, Kriti; Cram, Erin J.; Zaidel-Bar, Ronen

doi:10.1016/j.semcdb.2017.05.014

Cited by 23 publications

(19 citation statements)

References 101 publications

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“…In contrast, high stiffness allows the cell to resist deformation but could ultimately cause catastrophic rupture of the epithelial lining. Although the role of actomyosin and adhesion in promoting cell-intrinsic shape changes in single cells and epithelial sheets is well documented (Heisenberg and Bellaïche, 2013;Munjal and Lecuit, 2014;Harris, 2018;Röper, 2015;Takeichi, 2014), we have insufficient understanding of how cells resist or comply with external forces to balance cell, tissue and organ shape in vivo (Mao et al, 2013;Legoff et al, 2013;Mao and Baum, 2015;Ladoux and Mege, 2017;Sethi et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Response of epithelial cell and tissue shape to external forces in vivo

2019

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How actomyosin generates forces at epithelial adherens junctions has been extensively studied. However, less is known about how a balance between internal and external forces establishes epithelial cell, tissue and organ shape. We used the Drosophila egg chamber to investigate how contractility at adherens junctions in the follicle epithelium is modulated to accommodate and resist forces arising from the growing germ line. We found that between stages 6 and 9, adherens junction tension in the postmitotic epithelium decreases, suggesting that the junctional network relaxes to accommodate germline growth. At that time, a prominent medial Myosin II network coupled to corrugating adherens junctions develops. Local enrichment of medial Myosin II in main body follicle cells resists germline-derived forces, thus constraining apical areas and, consequently, cuboidal cell shapes at stage 9. At the tissue and organ level, local reinforcement of medial junction architecture ensures the timely contact of main body cells with the expanding oocyte and imposes circumferential constraints on the germ line guiding egg elongation. Our study provides insight into how adherens junction tension promotes cell and tissue shape transitions while integrating the growth and shape of an internally enclosed structure in vivo.

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Section: Introductionmentioning

confidence: 99%

Response of epithelial cell and tissue shape to external forces in vivo

2019

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“…Contraction of the spermatheca is driven by the well conserved Rho---ROCK and calcium signaling pathways, similar to those observed in non---muscle and smooth muscle cells (Brozovich et al, 2016;Pelaia et al, 2008;Sethi et al, 2017). These two pathways act in concert to regulate the levels of phosphorylated myosin (Somlyo and Somlyo, 2003).…”

Section: Introductionmentioning

confidence: 66%

“…Animals are full of biological tubing, including blood and lymphatic vessels, lung airways, salivary glands, digestive canals, and urinary and reproductive tracts. Actomyosin contractility plays a central role in the functioning of these biological tubes, which must dilate and contract with the proper timing and magnitude to generate appropriate responses to changing biological states (Reviewed in Sethi et al, 2017). Consequences of misregulated biological tubes can be seen in conditions such as heart disease, hypertension, and asthma (Lavoie et al, 2009;Seguchi et al, 2007;Uehata et al, 1997;Wettschureck and Offermanns, 2002).…”

Section: Introductionmentioning

confidence: 99%

The RhoGAP SPV-1 regulates calcium signaling to control the contractility of theC. elegansspermatheca during embryo transits

Bouffard

Cecchetelli

Clifford

et al. 2018

Preprint

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Running head: The RhoGAP SPV---1 regulates calcium signaling.Abbreviations used: RhoGAP, GTPase activating protein toward Rho family small GTPases; ROCK, Rho---associated protein kinase; sp---ut, spermatheca uterine valve.Highlight Summary: Through in vivo imaging of the calcium sensor GCaMP, we show that the RhoGAP SPV---1 is a key regulator of calcium signaling in the C. elegans spermatheca. Our data suggests SPV---1 acts at least partially through the small GTPase CDC---42 to modulate calcium signaling, while also acting on RHO---1 to modulate Rho---ROCK signaling. This places SPV---1 as a central regulator of cellular contractility. 1 AbstractContractility of the non---muscle and smooth muscle cells that comprise biological tubing is regulated by the Rho---ROCK and calcium signaling pathways. Although many molecular details about these signaling pathways are known, less is known about how they are coordinated spatiotemporally in biological tubes. The spermatheca of the C. elegans reproductive system enables study of the signaling pathways regulating actomyosin contractility in live adult animals. The RhoGAP SPV---1 was previously identified as a negative regulator of RHO---1/Rho and spermathecal contractility. Here, we uncover a role for SPV---1 as a key regulator of calcium signaling. spv---1 mutants expressing the calcium indicator GCaMP in the spermatheca exhibit premature calcium release, elevated calcium levels, and disrupted spatial regulation of calcium signaling during spermathecal contraction. Although RHO---1 is required for spermathecal contractility, RHO---1 does not play a significant role in regulating calcium. In contrast, activation of CDC---42 recapitulates many aspects of spv---1 mutant calcium signaling. Depletion of cdc---42 by RNAi does not suppress the premature or elevated calcium signal seen in spv---1 mutants, suggesting other targets remain to be identified. Our results suggest SPV---1 works through both the Rho---ROCK and calcium signaling pathways to coordinate cellular contractility.

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“…The signaling pathways that regulate acto-myosin contractility in the spermatheca are similar to those found in smooth muscle and non-muscle cells [13][14][15]. Two pathways, a Ca 2+ dependent and a Rho-dependent pathway are both necessary for spermathecal contractility.…”

Section: Introductionmentioning

confidence: 74%

Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in theCaenorhabditis elegansspermatheca

Castaneda

Cecchetelli

Pettit

et al. 2020

Preprint

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Correct regulation of cell contractility is critical for the function of many biological systems. The reproductive system of the hermaphroditic nematode C. elegans contains a contractile tube of myoepithelial cells known as the spermatheca, which stores sperm and is the site of oocyte fertilization. Regulated contraction of the spermatheca pushes the embryo into the uterus. Cell contractility in the spermatheca is dependent on actin and myosin and is regulated, in part, by Ca 2+ signaling through the phospholipase PLC-1, which mediates Ca 2+ release from the endoplasmic reticulum. Here, we describe a novel role for GSA-1/Gas, and protein kinase A, composed of the catalytic subunit KIN-1/PKA-C and the regulatory subunit KIN-2/PKA-R, in the regulation of Ca 2+ release and contractility in the C. elegans spermatheca. Without GSA-1/Gas or KIN-1/PKA-C, Ca 2+ is not released, and oocytes become trapped in the spermatheca. Conversely, when PKA is activated through either a gain of function allele in GSA-1 (GSA-1(GF)) or by depletion of KIN-2/PKA-R, Ca 2+ is increased, and waves of Ca 2+ travel across the spermatheca even in the absence of oocyte entry. In the spermathecal-uterine valve, loss of GSA-1/Gas or KIN-1/PKA-C results in sustained, high levels of Ca 2+ and a loss of coordination between the spermathecal bag and sp-ut valve. Additionally, we show that depleting phosphodiesterase PDE-6 levels alters contractility and Ca 2+ dynamics in the spermatheca, and that the GPB-1 and GPB-2 Gβ subunits play a central role in regulating spermathecal contractility and Ca 2+ signaling. This work identifies a signaling network in which Ca 2+ and cAMP pathways work together to coordinate spermathecal contractility. Author SummaryOrganisms are full of biological tubes that transport substances such as food, liquids, and air through the body. Moving these substances in a coordinated manner, with the correct directionality, timing, and rate is critical for organism health. In this study we used Caenorhabditis elegans, a small transparent worm, to study how cells in biological tubes coordinate how and when they squeeze and relax. The C. elegans spermatheca is part of the reproductive system, which uses calcium signaling to drive the coordinated contractions that push fertilized eggs out into the uterus. Using genetic analysis and a calcium-sensitive fluorescent protein, we show that the G-protein GSA-1 functions with protein kinase A to regulate calcium release, and contraction of the spermatheca. These findings establish a link between G-protein and cAMP signaling that may apply to similar signaling pathways in other systems.

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Stretch-induced actomyosin contraction in epithelial tubes: Mechanotransduction pathways for tubular homeostasis

Cited by 23 publications

References 101 publications

Response of epithelial cell and tissue shape to external forces in vivo

Response of epithelial cell and tissue shape to external forces in vivo

The RhoGAP SPV-1 regulates calcium signaling to control the contractility of theC. elegansspermatheca during embryo transits

Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in theCaenorhabditis elegansspermatheca

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