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1.
Cellular senescence is a process wherein proliferating cells undergo permanent cell cycle arrest while remaining viable. Senescence results in enhanced secretion of proteins that promote cancer and inflammation. We report here that the structure of the Golgi complex which regulates secretion is altered in senescent cells. In cells where senescence is achieved by replicative exhaustion or in cells wherein senescence has been induced with BrdU treatment dependent stress, the Golgi complex is dispersed. The expression of a G protein γ subunit, γ11, capable of translocation from the plasma membrane to the Golgi complex on receptor activation increases with senescence. Knockdown of γ11 or overexpression of a dominant negative γ3 subunit inhibits Golgi dispersal induced by senescence. Overall these results suggest that in cellular senescence an upregulated G protein gamma subunit mediates alterations in the structure of the Golgi. 相似文献
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Nitrogen is a major determinant of grain yield and quality. As excessive use of nitrogen fertilizer leads to environmental pollution and high production costs, improving nitrogen use efficiency (NUE) is fundamental for a sustainable agriculture. Here, we dissected the role of the barley abnormal cytokinin response1 repressor 1 (HvARE1) gene, a candidate for involvement in NUE previously identified in a genome-wide association study, through natural variation analysis and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing. HvARE1 was predominantly expressed in leaves and shoots, with very low expression in roots under low nitrogen conditions. Agrobacterium-mediated genetic transformation of immature embryos (cv. Golden Promise) with single guide RNAs targeting HvARE1 generated 22 T0 plants, from which four T1 lines harbored missense and/or frameshift mutations based on genotyping. Mutant are1 lines exhibited an increase in plant height, tiller number, grain protein content, and yield. Moreover, we observed a 1.5- to 2.8-fold increase in total chlorophyll content in the flag leaf at the grain filling stage. Delayed senescence by 10–14 d was also observed in mutant lines. Barley are1 mutants had high nitrogen content in shoots under low nitrogen conditions. These findings demonstrate the potential of ARE1 in NUE improvement in barley. 相似文献
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Mithila Tennakoon Kanishka Senarath Dinesh Kankanamge Deborah N. Chadee Ajith Karunarathne 《Molecular biology of the cell》2021,32(16):1446
G protein beta-gamma (Gβγ) subunits anchor to the plasma membrane (PM) through the carboxy-terminal (CT) prenyl group in Gγ. This interaction is crucial for the PM localization and functioning of Gβγ, allowing GPCR-G protein signaling to proceed. The diverse Gγ family has 12 members, and we have recently shown that the signaling efficacies of major Gβγ effectors are Gγ-type dependent. This dependency is due to the distinct series of membrane-interacting abilities of Gγ. However, the molecular process allowing for Gβγ subunits to exhibit a discrete and diverse range of Gγ-type–dependent membrane affinities is unclear and cannot be explained using only the type of prenylation. The present work explores the unique designs of membrane-interacting CT residues in Gγ as a major source for this Gγ-type–dependent Gβγ signaling. Despite the type of prenylation, the results show signaling efficacy at the PM, and associated cell behaviors of Gβγ are governed by crucially located specific amino acids in the five to six residue preprenylation region of Gγ. The provided molecular picture of Gγ–membrane interactions may explain how cells gain Gγ-type–dependent G protein-GPCR signaling as well as how Gβγ elicits selective signaling at various subcellular compartments. 相似文献
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Lopamudra Giri Anilkumar?K. Patel W.K.?Ajith Karunarathne Vani Kalyanaraman K.V. Venkatesh N. Gautam 《Biophysical journal》2014,107(1):242-254
G-protein βγ subunits translocate reversibly from the plasma membrane to internal membranes on receptor activation. Translocation rates differ depending on the γ subunit type. There is limited understanding of the role of the differential rates of Gβγ translocation in modulating signaling dynamics in a cell. Bifurcation analysis of the calcium oscillatory network structure predicts that the translocation rate of a signaling protein can regulate the damping of system oscillation. Here, we examined whether the Gβγ translocation rate regulates calcium oscillations induced by G-protein-coupled receptor activation. Oscillations in HeLa cells expressing γ subunit types with different translocation rates were imaged and quantitated. The results show that differential Gβγ translocation rates can underlie the diversity in damping characteristics of calcium oscillations among cells. Mathematical modeling shows that a translocation embedded motif regulates damping of G-protein-mediated calcium oscillations consistent with experimental data. The current study indicates that such a motif may act as a tuning mechanism to design oscillations with varying damping patterns by using intracellular translocation of a signaling component. 相似文献
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Lopamudra Giri Anilkumar K. Patel W.K. Ajith Karunarathne Vani Kalyanaraman K.V. Venkatesh N. Gautam 《Biophysical journal》2014
G-protein βγ subunits translocate reversibly from the plasma membrane to internal membranes on receptor activation. Translocation rates differ depending on the γ subunit type. There is limited understanding of the role of the differential rates of Gβγ translocation in modulating signaling dynamics in a cell. Bifurcation analysis of the calcium oscillatory network structure predicts that the translocation rate of a signaling protein can regulate the damping of system oscillation. Here, we examined whether the Gβγ translocation rate regulates calcium oscillations induced by G-protein-coupled receptor activation. Oscillations in HeLa cells expressing γ subunit types with different translocation rates were imaged and quantitated. The results show that differential Gβγ translocation rates can underlie the diversity in damping characteristics of calcium oscillations among cells. Mathematical modeling shows that a translocation embedded motif regulates damping of G-protein-mediated calcium oscillations consistent with experimental data. The current study indicates that such a motif may act as a tuning mechanism to design oscillations with varying damping patterns by using intracellular translocation of a signaling component. 相似文献
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Chamara A. Wijesinghe Shehan S. Williams Anuradhani Kasturiratne Nishantha Dolawaththa Piyal Wimalaratne Buddhika Wijewickrema Shaluka F. Jayamanne Geoffrey K. Isbister Andrew H. Dawson David G. Lalloo H. Janaka de Silva 《PLoS neglected tropical diseases》2015,9(8)
Background
Snakebite results in delayed psychological morbidity and negative psycho-social impact. However, psychological support is rarely provided to victims.Aim
To assess the effectiveness of a brief intervention which can be provided by non-specialist doctors aimed at reducing psychological morbidity following snakebite envenoming.Method
In a single blind, randomized controlled trial, snakebite victims with systemic envenoming [n = 225, 168 males, mean age 42.1 (SD 12.4) years] were randomized into three arms. One arm received no intervention (n = 68, Group A), the second received psychological first aid and psychoeducation (dispelling prevalent cultural beliefs related to snakebite which promote development of a sick role) at discharge from hospital (n = 65, Group B), while the third received psychological first aid and psychoeducation at discharge and a second intervention one month later based on cognitive behavioural principles (n = 69, Group C). All patients were assessed six months after hospital discharge for the presence of psychological symptoms and level of functioning using standardized tools.Results
At six months, there was a decreasing trend in the proportion of patients who were positive for psychiatric symptoms of depression and anxiety from Group A through Group B to Group C (Chi square test for trend = 7.901, p = 0.005). This was mainly due to a decreasing trend for symptoms of anxiety (chi-square for trend = 11.256, p = 0.001). There was also decreasing trend in the overall prevalence of disability from Group A through Group B to Group C (chi square for trend = 7.551, p = 0.006), predominantly in relation to disability in family life (p = 0.006) and social life (p = 0.005). However, there was no difference in the proportion of patients diagnosed with depression between the three groups (chi square for trend = 0.391, p = 0.532), and the intervention also had no effect on post-traumatic stress disorder.Conclusions
A brief psychological intervention, which included psychological first aid and psychoeducation plus cognitive behavioural therapy that can be provided by non-specialist doctors appeared to reduce psychiatric symptoms and disability after snakebite envenoming, but not depression or post-traumatic stress disorder.Trial Registration
Sri Lanka Clinical Trials Registry: SLCTR/2011/003 相似文献9.
Ajith Karunarathne WK O'Neill PR Martinez-Espinosa PL Kalyanaraman V Gautam N 《Biochemical and biophysical research communications》2012,421(3):605-611
Heterotrimeric G proteins transduce signals sensed by transmembrane G protein coupled receptors (GPCRs). A subfamily of G protein βγ subunit types has been shown to selectively translocate from the plasma membrane to internal membranes on receptor activation. Using 4D imaging we show here that Gβγ translocation is not restricted to some subunit types but rather all 12 members of the family of mammalian γ subunits are capable of supporting βγ translocation. Translocation kinetics varies widely depending on the specific γ subunit type, with t(1/2) ranging from 10s to many minutes. Using fluorescence complementation, we show that the β and γ subunits translocate as βγ dimers with kinetics determined by the γ subunit type. The expression patterns of endogenous γ subunit types in HeLa cells, hippocampal neurons and cardiomyocytes are distinctly different. Consistent with these differences, the βγ translocation rates vary widely. βγ translocation rates exhibit the same γ subunit dependent trends regardless of the specific receptor type or cell type showing that the translocation rates are intrinsic to the γ subunit types. βγ complexes with widely different rates of translocation had differential effects on muscarinic stimulation of GIRK channel activity. These results show that G protein βγ translocation is a general response to activation of GPCRs and may play a role in regulating signaling activity. 相似文献
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ABSTRACT: BACKGROUND: Cytomegalovirus associated transverse myelitis among immunocompetent adults has been rarely reported. We report a patient presenting with clinical myelitis followed by previously unreported finding of cytomegalovirus deoxyribonucleic acid in cerebrospinal fluid. Case report A forty year old immunocompetent male presented with acute onset progressive bilateral lower limb weakness. His spinal magnetic resonance imaging findings, cerebrospinal fluid analysis and clinical picture were compatible with transverse myelitis. Polymerase chain reaction of the cerebrospinal fluid for cytomegalovirus was positive while other infectious agents were not detected by serology or polymerase chain reaction. He was treated with intravenous ganciclovir with partial clinical response. CONCLUSION: Viral genome detection in the cerebrospinal fluid was performed but negative in five out of ten reported cases of cytomegalovirus associated transverse myelitis in the immunocompetent host. In previous cases the inability to isolate the virus in cerebrospinal fluid was considered favouring an immunological mechanism leading to pathogenesis rather than direct viral toxicity but this case is against that theory. This case highlights the fact that Cytomegalovirus should be considered as an aetiological agent in patients with transverse myelitis and that the virus may cause serious infections in immunocompetent host. Therefore this report is of importance to neurologists and physicians in general. 相似文献