Spatial control of active CDC-42 during collective migration of hypodermal cells in<i>Caenorhabditis elegans</i>

Ouellette, Marie-Hélène; Martin, Emmanuel; Lacoste-Caron, Germain; Hamiche, Karim; Jenna, Sarah

doi:10.1093/jmcb/mjv062

Cited by 23 publications

(35 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cdc42 has been reported not only to affect cell migration, but also to establish junctional complexes within collective migrating cells . For example, Cdc42 interacts with downstream protein complexes to regulate the formation of junctional proteins and maintain collective migration of hypodermal epithelial cells in Caenorhabditis elegans . Additionally, Cdc42 is activated by junctional proteins, P‐cadherins, to mediate collective migration in mesenchymal myoblasts .…”

Section: Discussionmentioning

confidence: 99%

“…21,22 For example, Cdc42 interacts with downstream protein complexes to regulate the formation of junctional proteins and maintain collective migration of hypodermal epithelial cells in Caenorhabditis elegans. 23 Additionally, Cdc42 is activated by junctional proteins, P-cadherins, to mediate collective migration in mesenchymal myoblasts. 24 In an- During lung development, Cdc42 directly regulates polarity and its activity is heightened at the active budding sides.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cdc42 regulates branching in angiogenic sprouting in vitro

et al. 2017

View full text Add to dashboard Cite

Objectives The morphogenetic events that occur during angiogenic sprouting involve several members of the Rho family of GTPases, including Cdc42. However, the precise roles of Cdc42 in angiogenic sprouting have been difficult to elucidate owing to the lack of models to study these events in vitro. Here, we aim to identify the roles of Cdc42 in branching morphogenesis in angiogenesis. Methods Using a 3D biomimetic model of angiogenesis in vitro, where endothelial cells were seeded inside a cylindrical channel within collagen gel and sprouted from the channel in response to a defined biochemical gradient of angiogenic factors, we inhibited Cdc42 activity with a small molecule inhibitor ML141 and examined the effects of Cdc42 on the morphogenetic processes of angiogenic sprouting. Results We find that partial inhibition of Cdc42 had minimal effects on directional migration of endothelial cells, but led to fewer branching events without affecting the length of these branches. We also observed that antagonizing Cdc42 reduced collective migration in favor of single cell migration. Additionally, Cdc42 also regulated the initiation of filopodial extensions in endothelial tip cells. Conclusions Our findings suggest that Cdc42 can affect multiple morphogenetic processes during angiogenic sprouting and ultimately impact the architecture of the vasculature.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cdc42 regulates branching in angiogenic sprouting in vitro

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Ouellette and colleagues showed decreased dynamics in wsp-1 mutants, measured as how much the leading-edge membrane is displaced in the leading cells ( [21]Ouellette et al, 2016), although they did not examine F-actin levels. In contrast, we examined the dynamic formation of protrusion and retractions at the leading edge.…”

Section: Protrusions Dynamics Are Not Significantly Affected By the Cmentioning

confidence: 99%

RhoGAP RGA-8 supports morphogenesis inC. elegansby polarizing epithelia through CDC-42

Raduwan¹,

Sasidharan²,

Burgos³

et al. 2019

Preprint

View full text Add to dashboard Cite

RGA-8, a protein with membrane binding and actin regulatory motifs, promotes embryonic morphogenesis by localizing active CDC-42 in developing epithelia, thus controlling actin and actin motors during cell movements. Abstract -CDC-42 regulation of non-muscle myosin/ NMY-2 is required for polarity maintenance in the one-cell embryo of C. elegans. CDC-42 and NMY-2 regulate polarity throughout embryogenesis, but their contribution to later events of morphogenesis are less understood.We have shown that epidermal enclosure requires the GTPase CED-10/Rac1 and WAVE/Scar complex, its effector, to promote protrusions that drive enclosure through the branch actin regulator Arp2/3. Our analysis here of RGA-8, a homolog of SH3BP1/Rich1/ARHGAP17/Nadrin, with BAR and RhoGAP motifs, suggests it regulates CDC-42, so that NMY-2 promotes two events of epidermal morphogenesis: ventral enclosure and elongation. Genetic and molecular data suggest RGA-8 regulates CDC-42, and the CDC-42 effectors WSP-1 and MRCK-1, in parallel to F-BAR proteins TOCA-1 and TOCA-2.The RGA-8-CDC-42-WSP-1 pathway enriches myosin in migrating epidermal cells during ventral enclosure. We propose TOCA proteins and RGA-8 use BAR domains to localize and regenerate CDC-42 activity, thus regulating F-actin levels, through the branched actin regulator WSP-1, and myosin polarity through the myosin kinase MRCK-1. Regulated CDC-42 thus polarizes epithelia, to control cell migrations and cell shape changes of embryonic morphogenesis.

show abstract

“…Regulation of cellular contractility and relaxation is essential for the function of epithelial and endothelial tubes, which are subjected to changing flow, strain, and pressure as they transport liquid, gases, and other cells throughout the body [1,2]. The Caenorhabditis elegans spermatheca, part of the hermaphroditic reproductive system, is an excellent model for the study of coordinated cell contractility [3][4][5][6][7][8]. The C. elegans reproductive system is composed of two symmetrical gonad arms surrounded by smooth muscle-like sheath cells, the spermathecae, and a common uterus [9,10].…”

Section: Introductionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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.

show abstract

Spatial control of active CDC-42 during collective migration of hypodermal cells inCaenorhabditis elegans

Cited by 23 publications

References 44 publications

Cdc42 regulates branching in angiogenic sprouting in vitro

Cdc42 regulates branching in angiogenic sprouting in vitro

RhoGAP RGA-8 supports morphogenesis inC. elegansby polarizing epithelia through CDC-42

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

Contact Info

Product

Resources

About