Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase

Kaneko-Kawano, Takako; Takasu, Fugo; Naoki, Honda; Sakumura, Yuichi; Ishii, Shin; Ueba, Takahiro; Eiyama, Akinori; Okada, Aiko; Kawano, Yoji; Suzuki, Kenji

doi:10.1371/journal.pone.0039269

Cited by 53 publications

(48 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rho-associated kinase (ROCK) is a known Rho effector protein and it may act to increase cytoskeletal tension by directly or indirectly facilitating the phosphorylation of myosin light chain [55]. To investigate if ROCK inhibition could stimulate a restoration in cell spreading, Y27632 and thiazovivin, two known ROCK inhibitors [56,57], were used to treat B16/GPR4 cells.…”

Section: Discussionmentioning

confidence: 99%

GPR4 decreases B16F10 melanoma cell spreading and regulates focal adhesion dynamics through the G13/Rho signaling pathway

Justus

Yang

2015

Experimental Cell Research

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

GPR4 decreases B16F10 melanoma cell spreading and regulates focal adhesion dynamics through the G13/Rho signaling pathway

Justus

Yang

2015

Experimental Cell Research

View full text Add to dashboard Cite

“…The concentration of RhoK is taken to be fixed at 30 nM (29), except in the presence of specific inhibitors.…”

Section: Rho-kinase Inhibition Of Mlcpmentioning

confidence: 99%

Calcium dynamics underlying the myogenic response of the renal afferent arteriole

Edwards

2014

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

The renal afferent arteriole reacts to an elevation in blood pressure with an increase in muscle tone and a decrease in luminal diameter. This effect, known as the myogenic response, is believed to stabilize glomerular filtration and to protect the glomerulus from systolic blood pressure increases, especially in hypertension. To study the mechanisms underlying the myogenic response, we developed a mathematical model of intracellular Ca(2+) signaling in an afferent arteriole smooth muscle cell. The model represents detailed transmembrane ionic transport, intracellular Ca(2+) dynamics, the kinetics of myosin light chain phosphorylation, and the mechanical behavior of the cell. It assumes that the myogenic response is initiated by pressure-induced changes in the activity of nonselective cation channels. Our model predicts spontaneous vasomotion at physiological luminal pressures and KCl- and diltiazem-induced diameter changes comparable to experimental findings. The time-periodic oscillations stem from the dynamic exchange of Ca(2+) between the cytosol and the sarcoplasmic reticulum, coupled to the stimulation of Ca(2+)-activated potassium (KCa) and chloride (ClCa) channels, and the modulation of voltage-activated L-type channels; blocking sarco/endoplasmic reticulum Ca(2+) pumps, ryanodine receptors (RyR), KCa, ClCa, or L-type channels abolishes these oscillations. Our results indicate that the profile of the myogenic response is also strongly dependent on the conductance of ClCa and L-type channels, as well as the activity of plasmalemmal Ca(2+) pumps. Furthermore, inhibition of KCa is not necessary to induce myogenic contraction. Lastly, our model suggests that the kinetic behavior of L-type channels results in myogenic kinetics that are substantially faster during constriction than during dilation, consistent with in vitro observations (Loutzenhiser R, Bidani A, Chilton L. Circ. Res. 90: 1316-1324, 2002).

show abstract

“…52, and for large barbed end density or the "coherent" regime, the protrusion rate is not sensitive to the number of barbed ends. We also assume that the Rho-activation leads to the activation of ROCK and myosin phosphorylation (53). We then propose that the increase in spine size is proportional to the increase in actin barbed ends (similar to the leading edge pushing velocity) and that the decrease is proportional to the amount of phosphorylated myosin.…”

Section: Spine Volume Change In Response To Calcium Influx As a Nestedmentioning

confidence: 99%

Paradoxical signaling regulates structural plasticity in dendritic spines

Rangamani

Levy

Khan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Transient spine enlargement (3-to 5-min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks, and their role is to control both the activation and the inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion, including calmodulin-dependent protein kinase II (CaMKII), RhoA, and Cdc42, and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics.CaMKII | dendritic spine | actin

show abstract

Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase

Cited by 53 publications

References 50 publications

GPR4 decreases B16F10 melanoma cell spreading and regulates focal adhesion dynamics through the G13/Rho signaling pathway

GPR4 decreases B16F10 melanoma cell spreading and regulates focal adhesion dynamics through the G13/Rho signaling pathway

Calcium dynamics underlying the myogenic response of the renal afferent arteriole

Paradoxical signaling regulates structural plasticity in dendritic spines

Contact Info

Product

Resources

About