scholarly journals The RhoGAP SPV-1 regulates calcium signaling to control the contractility of theCaenorhabditis elegansspermatheca during embryo transits

2019 ◽  
Vol 30 (7) ◽  
pp. 907-922 ◽  
Author(s):  
Jeff Bouffard ◽  
Alyssa D. Cecchetelli ◽  
Coleman Clifford ◽  
Kriti Sethi ◽  
Ronen Zaidel-Bar ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathways ◽  
Calcium Release ◽  
Small Gtpases ◽  
Negative Regulator ◽  
Calcium Signal ◽  
Spatial Regulation ◽  
Actomyosin Contractility ◽  
Calcium Indicator ◽  
Rho Family

Contractility of the nonmuscle and smooth muscle cells that comprise biological tubing is regulated by the Rho-ROCK (Rho-associated protein kinase) 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 Caenorhabditis elegans reproductive system enables study of the signaling pathways regulating actomyosin contractility in live adult animals. The RhoGAP (GTPase-­activating protein toward Rho family small GTPases) 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 RNA interference does not suppress the premature or elevated calcium signal seen in spv-1 mutants, suggesting other targets remain to be identified. Our results suggest that SPV-1 works through both the Rho-ROCK and calcium signaling pathways to coordinate cellular contractility.

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

2018 ◽  
Author(s):  
Jeff Bouffard ◽  
Alyssa D. Cecchetelli ◽  
Coleman Clifford ◽  
Kriti Sethi ◽  
Ronen Zaidel-Bar ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathways ◽  
Calcium Release ◽  
Small Gtpase ◽  
Negative Regulator ◽  
Calcium Signal ◽  
C Elegans ◽  
Spatial Regulation ◽  
Calcium Indicator

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 theC. elegansreproductive 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-1mutants 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 ofspv-1mutant calcium signaling. Depletion ofcdc-42by RNAi does not suppress the premature or elevated calcium signal seen inspv-1mutants, 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.Highlight SummaryThroughin vivoimaging of the calcium sensor GCaMP, we show that the RhoGAP SPV-1 is a key regulator of calcium signaling in theC. elegansspermatheca. 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.

Adenine-based calcium signal pathway messengers: Synthesis and agonistic properties of cyclic ADP-ribose analogs

2008 ◽  
Vol 80 (8) ◽  
pp. 1821-1825
Author(s):  
Liangren Zhang ◽  
Zhenjun Yang ◽  
Andreas H. Guse ◽  
Lihe Zhang
Keyword(s):  
T Lymphocytes ◽  
Calcium Signaling ◽  
Molecular Mechanism ◽  
Calcium Release ◽  
Biological Activities ◽  
Signal Pathway ◽  
Calcium Signal ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Cyclic Adp Ribose

A series of cyclic ADP-ribose (cADPR) analogs, in which modifications mainly focused on riboses, was synthesized in order to explore the molecular mechanism of calcium release regulated by cADPR. Biological activities investigated in intact T-lymphocytes showed that the structurally simplified analogs, N1-ethoxymethyl-substituted cyclic inosine diphosphoribose (cIDPRE), N1,N9-diethoxymethyl-substituted cyclic inosine diphosphoribose (cIDPDE), and N1-ethoxymethyl-substituted cyclic adenosine diphosphoribose (cADPRE) in which the northern ribose or both northern and southern riboses were replaced by ether linkages are membrane-permeant and induce calcium release from intracellular stores. This research has provided novel molecules to probe cADPR-mediated calcium signaling and enlarges our knowledge of the structure-activity relationships of cADPR analogs.

scholarly journals The PAK system links Rho GTPase signaling to thrombin-mediated platelet activation

2013 ◽  
Vol 305 (5) ◽  
pp. C519-C528 ◽  
Author(s):  
Joseph E. Aslan ◽  
Sandra M. Baker ◽  
Cassandra P. Loren ◽  
Kristina M. Haley ◽  
Asako Itakura ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Platelet Activation ◽  
Rho Gtpase ◽  
Regulatory Protein ◽  
Small Gtpases ◽  
Mass Spectrometry Analysis ◽  
Actin Dynamics ◽  
Nucleotide Exchange ◽  
Spectrometry Analysis ◽  
Rho Family

Regulation of the platelet actin cytoskeleton by the Rho family of small GTPases is essential for the proper maintenance of hemostasis. However, little is known about how intracellular platelet activation from Rho GTPase family members, including Rac, Cdc42, and Rho, translate into changes in platelet actin structures. To better understand how Rho family GTPases coordinate platelet activation, we identified platelet proteins associated with Rac1, a Rho GTPase family member, and actin regulatory protein essential for platelet hemostatic function. Mass spectrometry analysis revealed that upon platelet activation with thrombin, Rac1 associates with a set of effectors of the p21-activated kinases (PAKs), including GIT1, βPIX, and guanine nucleotide exchange factor GEFH1. Platelet activation by thrombin triggered the PAK-dependent phosphorylation of GIT1, GEFH1, and other PAK effectors, including LIMK1 and Merlin. PAK was also required for the thrombin-mediated activation of the MEK/ERK pathway, Akt, calcium signaling, and phosphatidylserine (PS) exposure. Inhibition of PAK signaling prevented thrombin-induced platelet aggregation and blocked platelet focal adhesion and lamellipodia formation in response to thrombin. Together, these results demonstrate that the PAK signaling system is a key orchestrator of platelet actin dynamics, linking Rho GTPase activation downstream of thrombin stimulation to PAK effector function, MAP kinase activation, calcium signaling, and PS exposure in platelets.

scholarly journals DRhoGEF2 regulates actin organization and contractility in the Drosophila blastoderm embryo

2005 ◽  
Vol 168 (4) ◽  
pp. 575-585 ◽  
Author(s):  
Mojgan Padash Barmchi ◽  
Stephen Rogers ◽  
Udo Häcker
Keyword(s):  
Cell Shape ◽  
Cell Formation ◽  
Small Gtpases ◽  
Actin Organization ◽  
Actomyosin Contractility ◽  
Pole Cell ◽  
Rho Family ◽  
Cytoskeletal Function ◽  
Actin Rings ◽  
Shape Changes

Morphogenesis of the Drosophila melanogaster embryo is associated with a dynamic reorganization of the actin cytoskeleton that is mediated by small GTPases of the Rho family. Often, Rho1 controls different aspects of cytoskeletal function in parallel, requiring a complex level of regulation. We show that the guanine triphosphate (GTP) exchange factor DRhoGEF2 is apically localized in epithelial cells throughout embryogenesis. We demonstrate that DRhoGEF2, which has previously been shown to regulate cell shape changes during gastrulation, recruits Rho1 to actin rings and regulates actin distribution and actomyosin contractility during nuclear divisions, pole cell formation, and cellularization of syncytial blastoderm embryos. We propose that DRhoGEF2 activity coordinates contractile actomyosin forces throughout morphogenesis in Drosophila by regulating the association of myosin with actin to form contractile cables. Our results support the hypothesis that specific aspects of Rho1 function are regulated by specific GTP exchange factors.

scholarly journals Calcium signaling mediates mechanotransduction at the multicellular stage of Dictyostelium discoideum

2021 ◽  
Author(s):  
Hidenori Hashimura ◽  
Yusuke V. Morimoto ◽  
Yusei Hirayama ◽  
Masahiro Ueda
Keyword(s):  
Calcium Signaling ◽  
Dictyostelium Discoideum ◽  
Molecular Mechanisms ◽  
Calcium Release ◽  
Calcium Influx ◽  
Cytosolic Calcium ◽  
Calcium Signal ◽  
Mechanical Stimuli ◽  
Ip3 Receptor ◽  
Cellular Functions

Calcium acts as a second messenger and regulates cellular functions, including cell motility. In Dictyostelium discoideum, the cytosolic calcium level oscillates synchronously, and calcium signal waves propagate in the cell population during the early stages of development, including aggregation. At the unicellular phase, the calcium response through Piezo channels also functions in mechanosensing. However, calcium signaling dynamics during multicellular morphogenesis is still unclear. Here, live-imaging of cytosolic calcium levels revealed that calcium wave propagation, depending on cAMP relay, temporarily disappeared at the onset of multicellular body formation. Alternatively, the occasional burst of calcium signals and their propagation were observed in both anterior and posterior regions of migrating multicellular bodies. Calcium signaling in multicellular bodies occurred in response to mechanical stimulation. Both pathways, calcium release from the endoplasmic reticulum via IP3 receptor and calcium influx from outside the cell, were involved in calcium waves induced by mechanical stimuli. These show that calcium signaling works on mechanosensing in both the unicellular and multicellular phases of Dictyostelium using different molecular mechanisms during development.

scholarly journals The Small GTPase Rap1b: A Bidirectional Regulator of Platelet Adhesion Receptors

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Gianni Francesco Guidetti ◽  
Mauro Torti
Keyword(s):  
Cell Adhesion ◽  
Signaling Pathways ◽  
Platelet Adhesion ◽  
Thrombus Formation ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Complex Pattern ◽  
Adhesive Properties ◽  
Adhesion Receptors ◽  
Inside Out

Integrins and other families of cell adhesion receptors are responsible for platelet adhesion and aggregation, which are essential steps for physiological haemostasis, as well as for the development of thrombosis. The modulation of platelet adhesive properties is the result of a complex pattern of inside-out and outside-in signaling pathways, in which the members of the Rap family of small GTPases are bidirectionally involved. This paper focuses on the regulation of the main Rap GTPase expressed in circulating platelets, Rap1b, downstream of adhesion receptors, and summarizes the most recent achievements in the investigation of the function of this protein as regulator of platelet adhesion and thrombus formation.

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