scholarly journals Sticky/Citron kinase maintains proper RhoA localization at the cleavage site during cytokinesis

2011 ◽  
Vol 195 (4) ◽  
pp. 595-603 ◽  
Author(s):  
Zuni I. Bassi ◽  
Koen J. Verbrugghe ◽  
Luisa Capalbo ◽  
Stephen Gregory ◽  
Emilie Montembault ◽  
...  
Keyword(s):  
Cleavage Site ◽  
Kinase Activity ◽  
Rho Kinase ◽  
Compact Ring ◽  
Contractile Ring ◽  
Rhoa Activity ◽  
Ring Dynamics ◽  
Citron Kinase ◽  
Guanosine Triphosphatase

In many organisms, the small guanosine triphosphatase RhoA controls assembly and contraction of the actomyosin ring during cytokinesis by activating different effectors. Although the role of some RhoA effectors like formins and Rho kinase is reasonably understood, the functions of another putative effector, Citron kinase (CIT-K), are still debated. In this paper, we show that, contrary to previous models, the Drosophila melanogaster CIT-K orthologue Sticky (Sti) does not require interaction with RhoA to localize to the cleavage site. Instead, RhoA fails to form a compact ring in late cytokinesis after Sti depletion, and this function requires Sti kinase activity. Moreover, we found that the Sti Citron-Nik1 homology domain interacts with RhoA regardless of its status, indicating that Sti is not a canonical RhoA effector. Finally, Sti depletion caused an increase of phosphorylated myosin regulatory light chain at the cleavage site in late cytokinesis. We propose that Sti/CIT-K maintains correct RhoA localization at the cleavage site, which is necessary for proper RhoA activity and contractile ring dynamics.

Abstract 270: Rnd3/RhoE Haploinsufficient Mice are Hypersensitive to Pressure Overload and Develop Apoptotic Cardiomyopathy with Heart Failure

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Xiaojing Yue ◽  
Xiangsheng Yang ◽  
Xi Lin ◽  
Tingli Yang ◽  
Xin Yi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Kinase Activity ◽  
Rho Gtpase ◽  
Coiled Coil ◽  
Rho Kinase ◽  
Pressure Overload ◽  
Small Gtpase ◽  
Loss Of Function ◽  
Double Knockout ◽  
Guanosine Triphosphatase

Rationale: Rho family guanosine triphosphatase (GTPase) 3 (Rnd3, also called RhoE), a member of the small Rho GTPase family, has been suggested to regulate cell actin cytoskeleton dynamics, cell migration, and apoptosis through the Rho kinase-dependent signaling pathway. The biological function of Rnd3 in the heart is unknown. The downregulation of small GTPase Rnd3 transcripts was found in patients with end-stage heart failure. The pathological significance of Rnd3 loss in the transition to heart failure remains unexplored. Objective: To investigate the functional consequence of Rnd3 downregulation and the associated molecular mechanism. Methods and Results: we generated Rnd3 +/- haploinsufficient mice to mimic the downregulation of Rnd3 observed in the failing human heart. Rnd3 +/- mice were viable; however, the mice developed heart failure after pressure overload by transverse aortic constriction (TAC). Remarkable apoptosis, increased caspase-3 activity, and elevated Rho kinase activity were detected in the Rnd3 +/- haploinsufficient animal hearts. Pharmacological inhibition of Rho kinase by Fasudil treatment partially improved Rnd3 +/- mouse cardiac functions and attenuated myocardial apoptosis. To determine if Rho associated coiled-coil kinase 1 (ROCK1) was responsible for Rnd3 deficiency-mediated apoptotic cardiomyopathy, we established a double knockout mouse line, the Rnd3 haploinsufficient mice with ROCK1-null background (Rnd3 +/-/ROCK1-/- ). Again, genetic deletion of ROCK1 partially but not completely rescued Rnd3 deficiency-mediated heart failure phenotype. Conclusion: Downregulation of Rnd3 correlates with cardiac loss of function as in heart failure patients. Hyperactivation of Rho kinase activity is responsible in part for the apoptotic cardiomyopathy development. Further investigation of ROCK1-independent mechanisms in Rnd3-mediated cardiac remodeling should be the focus for future study.

scholarly journals Drosophila Citron Kinase Is Required for the Final Steps of Cytokinesis

2004 ◽  
Vol 15 (11) ◽  
pp. 5053-5063 ◽  
Author(s):  
Valeria Naim ◽  
Sara Imarisio ◽  
Ferdinando Di Cunto ◽  
Maurizio Gatti ◽  
Silvia Bonaccorsi
Keyword(s):  
Rna Interference ◽  
Cleavage Site ◽  
Cell Types ◽  
Wild Type ◽  
Contractile Ring ◽  
Type Function ◽  
Central Spindle ◽  
Intercellular Bridges ◽  
Membrane Protrusions ◽  
Citron Kinase

The mechanisms underlying completion of cytokinesis are still poorly understood. Here, we show that the Drosophila orthologue of mammalian Citron kinases is essential for the final events of the cytokinetic process. Flies bearing mutations in the Drosophila citron kinase (dck) gene were defective in both neuroblast and spermatocyte cytokinesis. In both cell types, early cytokinetic events such as central spindle assembly and contractile ring formation were completely normal. Moreover, cytokinetic rings constricted normally, leading to complete furrow ingression. However late telophases of both cell types displayed persistent midbodies associated with disorganized F actin and anillin structures. Similar defects were observed in dck RNA interference (RNAi) telophases, which, in addition to abnormal F actin and anillin rings, also displayed aberrant membrane protrusions at the cleavage site. Together, these results indicate that mutations in the dck gene result in morphologically abnormal intercellular bridges and in delayed resolution of these structures, suggesting that the wild-type function of dck is required for abscission at the end of cytokinesis. The phenotype of Dck-depleted cells is different from those observed in most Drosophila cytokinesis mutants but extraordinarily similar to that caused by anillin RNAi, suggesting that Dck and anillin are in the same pathway for completion of cytokinesis.

scholarly journals Ibuprofen Protects Ventilator-Induced Lung Injury by Downregulating Rho-Kinase Activity in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Liang-Ti Huang ◽  
Chien-Huang Lin ◽  
Hsiu-Chu Chou ◽  
Chung-Ming Chen
Keyword(s):  
Lung Injury ◽  
Protein Expression ◽  
Tidal Volume ◽  
Kinase Activity ◽  
Rho Kinase ◽  
Weight Ratio ◽  
Dry Weight ◽  
High Tidal Volume ◽  
Rhoa Activity ◽  
Ventilator Induced Lung Injury

Background. Ventilator-induced lung injury-(VILI-) induced endothelial permeability is regulated through the Rho-dependent signaling pathway. Ibuprofen inhibits Rho activation in animal models of spinal-cord injury and Alzheimer’s disease. The study aims to investigate ibuprofen effects on high tidal volume associated VILI.Methods. Twenty-eight adult male Sprague-Dawley rats were randomized to receive a ventilation strategy with three different interventions for 2 h: (1) a high-volume zero-positive end-expiratory pressure (PEEP) (HVZP) group; (2) an HVZP + ibuprofen 15 mg/kg group; and (3) an HVZP + ibuprofen 30 mg/kg group. A fourth group without ventilation served as the control group. Rho-kinase activity was determined by ratio of phosphorylated ezrin, radixin, and moesin (p-ERM), substrates of Rho-kinase, to total ERM. VILI was characterized by increased pulmonary protein leak, wet-to-dry weight ratio, cytokines level, and Rho guanine nucleotide exchange factor (GEF-H1), RhoA activity, p-ERM/total ERM, and p-myosin light chain (MLC) protein expression.Results. Ibuprofen pretreatment significantly reduced the HVZP ventilation-induced increase in pulmonary protein leak, wet-to-dry weight ratio, bronchoalveolar lavage fluid interleukin-6 and RANTES levels, and lung GEF-H1, RhoA activity, p-ERM/total ERM, and p-MLC protein expression.Conclusion. Ibuprofen attenuated high tidal volume induced pulmonary endothelial hyperpermeability. This protective effect was associated with a reduced Rho-kinase activity.

scholarly journals Peroxynitrite Mediates Diabetes-Induced Endothelial Dysfunction: Possible Role of Rho Kinase Activation

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Azza B. El-Remessy ◽  
Huda E. Tawfik ◽  
Suraporn Matragoon ◽  
Bindu Pillai ◽  
Ruth B. Caldwell ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Lipid Peroxides ◽  
Enos Expression ◽  
Aortic Endothelial Cells ◽  
Rhoa Activity ◽  
Stress Markers ◽  
Enos Mrna

Endothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15 mg/Kg/day) for 4 weeks. Vasorelaxation to acetylcholine, oxidative-stress markers, RhoA activity, and eNOS expression were determined. Diabetic coronary arteries showed significant reduction in ACh-mediated maximal relaxation compared to controls. Diabetic vessels showed also significant increases in lipid-peroxides, nitrotyrosine, and active RhoA and 50% reduction in eNOS mRNA expression. Treatment of diabetic animals with FeTTPS blocked these effects. Studies in aortic endothelial cells show that high glucose or peroxynitrite increases the active RhoA kinase levels and decreases eNOS expression and NO levels, which were reversed with blocking peroxynitrite or Rho kinase. Together, peroxynitrite can suppress eNOS expression via activation of RhoA and hence cause vascular dysfunction.

scholarly journals Role of rho-kinase activity in angiotensin II-induced contraction of rabbit clitoral cavernosum smooth muscle

2002 ◽  
Vol 14 (6) ◽  
pp. 472-477 ◽  
Author(s):  
J K Park ◽  
S O Lee ◽  
Y G Kim ◽  
S H Kim ◽  
G Y Koh ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Kinase Activity ◽  
Rho Kinase

scholarly journals Differential regulation of muscarinic M2 and M3 receptor signaling in gastrointestinal smooth muscle by caveolin-1

2013 ◽  
Vol 305 (3) ◽  
pp. C334-C347 ◽  
Author(s):  
Sayak Bhattacharya ◽  
Sunila Mahavadi ◽  
Othman Al-Shboul ◽  
Senthilkumar Rajagopal ◽  
John R. Grider ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Kinase Activity ◽  
Rho Kinase ◽  
Receptor Signaling ◽  
Caveolin 1 ◽  
Pi Hydrolysis ◽  
G Protein Coupled ◽  
Stimulation Of

Caveolae act as scaffolding proteins for several G protein-coupled receptor signaling molecules to regulate their activity. Caveolin-1, the predominant isoform in smooth muscle, drives the formation of caveolae. The precise role of caveolin-1 and caveolae as scaffolds for G protein-coupled receptor signaling and contraction in gastrointestinal muscle is unclear. Thus the aim of this study was to examine the role of caveolin-1 in the regulation of Gq- and Gi-coupled receptor signaling. RT-PCR, Western blot, and radioligand-binding studies demonstrated the selective expression of M2 and M3 receptors in gastric smooth muscle cells. Carbachol (CCh) stimulated phosphatidylinositol (PI) hydrolysis, Rho kinase and zipper-interacting protein (ZIP) kinase activity, induced myosin phosphatase 1 (MYPT1) phosphorylation (at Thr696) and 20-kDa myosin light chain (MLC20) phosphorylation (at Ser19) and muscle contraction, and inhibited cAMP formation. Stimulation of PI hydrolysis, Rho kinase, and ZIP kinase activity, phosphorylation of MYPT1 and MLC20, and muscle contraction in response to CCh were attenuated by methyl β-cyclodextrin (MβCD) or caveolin-1 small interfering RNA (siRNA). Similar inhibition of PI hydrolysis, Rho kinase, and ZIP kinase activity and muscle contraction in response to CCh and gastric emptying in vivo was obtained in caveolin-1-knockout mice compared with wild-type mice. Agonist-induced internalization of M2, but not M3, receptors was blocked by MβCD or caveolin-1 siRNA. Stimulation of PI hydrolysis, Rho kinase, and ZIP kinase activities in response to other Gq-coupled receptor agonists such as histamine and substance P was also attenuated by MβCD or caveolin-1 siRNA. Taken together, these results suggest that caveolin-1 facilitates signaling by Gq-coupled receptors and contributes to enhanced smooth muscle function.

scholarly journals Role of Rho‐Kinase Activity and Expression in the Ductus Arteriosus in the Chicken Embryo

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Adrian G Cadar ◽  
Tushar S Sirsat ◽  
Edward M Dzialowski
Keyword(s):  
Chicken Embryo ◽  
Kinase Activity ◽  
Ductus Arteriosus ◽  
Rho Kinase

142-OR: Unique Role of the a4 Component for S6-Kinase Activity in Metabolic Regulation and Anti-apoptotic Effect in Brown Adipose Tissue

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 142-OR
Author(s):  
MASAJI SAKAGUCHI ◽  
SHOTA OKAGAWA ◽  
SAYAKA KITANO ◽  
TATSUYA KONDO ◽  
EIICHI ARAKI
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Metabolic Regulation ◽  
Kinase Activity ◽  
S6 Kinase ◽  
Unique Role ◽  
Brown Adipose ◽  
Apoptotic Effect

Effect of Early Normotension with Olmesartan on Rho-kinase Activity in Hypertensive Patients

2019 ◽  
Vol 18 (1) ◽  
pp. 87-91 ◽  
Author(s):  
Claudio Cantin ◽  
Jorge E. Jalil ◽  
Juan F. Bulnes ◽  
Ulises Novoa ◽  
Paul MacNab ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Kinase Activity ◽  
Clinical Evidence ◽  
Mononuclear Cells ◽  
Treatment Initiation ◽  
Rho Kinase ◽  
Angiotensin Ii Receptor ◽  
Peripheral Blood Mononuclear ◽  
Hypertensive Patients ◽  
Rock Activity

Background: Angiotensin II is a potent activator of the Rho-kinase (ROCK) pathway, through which it exerts some of its adverse vasoconstrictor effects. Clinical evidence on the effects of blocking the angiotensin II receptor 1 on ROCK activity in hypertensive patients is scarce. Objective: To demonstrate that ROCK activity in peripheral blood mononuclear cells (PMBCs) in patients with essential hypertension is reduced earlier than previously observed, along with blood pressure (BP) lowering on treatment with olmesartan. Methods: Prospective pilot open study; 17 hypertensive patients were treated with progressive olmesartan doses starting with 20 mg qd. BP was measured at 3, 6 and 9 weeks after treatment initiation. If treatment failed to normalize BP after 3 weeks, olmesartan dose was increased to 40 mg qd, and if still hypertensive after 6 weeks, 12.5 mg of hydrochlorothiazide qd was added. ROCK activity was measured at baseline and 9 weeks after treatment as myosin phosphatase target subunit 1 phosphorylation (MYPT1-p/T ratio) in PBMC. Results: Mean baseline BP was 162 ± 4.9/101 ± 2.4 mmHg. After 9 weeks of treatment, both systolic and diastolic BP were reduced by 41 and 22 mmHg, respectively (p<0.05). Mean pretreatment MYPT1- p/T ratio in PMBCs was significantly reduced by 80% after 9 weeks with olmesartan (p<0.01). Conclusion: Normotension achieved after 9 weeks in 82% of the patients treated with olmesartan was associated with a significant reduction of ROCK activity in PBMC.

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