scholarly journals An endogenous chemorepellent directs cell movement by inhibiting pseudopods at one side of cells

2019 ◽  
Vol 30 (2) ◽  
pp. 242-255 ◽  
Author(s):  
Ramesh Rijal ◽  
Kristen M. Consalvo ◽  
Christopher K. Lindsey ◽  
Richard H. Gomer
Keyword(s):  
Signal Transduction ◽  
Actin Polymerization ◽  
Formation Rate ◽  
Cell Movement ◽  
Signal Transduction Pathway ◽  
Pi3 Kinase ◽  
Signal Transduction Pathways ◽  
Ras Protein ◽  
A Cell ◽  
G Protein Coupled

Eukaryotic chemoattraction signal transduction pathways, such as those used by Dictyostelium discoideum to move toward cAMP, use a G protein–coupled receptor to activate multiple conserved pathways such as PI3 kinase/Akt/PKB to induce actin polymerization and pseudopod formation at the front of a cell, and PTEN to localize myosin II to the rear of a cell. Relatively little is known about chemorepulsion. We previously found that AprA is a chemorepellent protein secreted by Dictyostelium cells. Here we used 29 cell lines with disruptions of cAMP and/or AprA signal transduction pathway components, and delineated the AprA chemorepulsion pathway. We find that AprA uses a subset of chemoattraction signal transduction pathways including Ras, protein kinase A, target of rapamycin (TOR), phospholipase A, and ERK1, but does not require the PI3 kinase/Akt/PKB and guanylyl cyclase pathways to induce chemorepulsion. Possibly as a result of not using the PI3 kinase/Akt/PKB pathway and guanylyl cyclases, AprA does not induce actin polymerization or increase the pseudopod formation rate, but rather appears to inhibit pseudopod formation at the side of cells closest to the source of AprA.

The Phosphoinositide Signal Transduction Pathway in the Pathogenesis of Alzheimer’s Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 355-362 ◽  
Author(s):  
Vincenza Rita Lo Vasco
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signal Transduction ◽  
Membrane Trafficking ◽  
Hormone Secretion ◽  
Signal Transduction Pathway ◽  
Brain Morphology ◽  
Signal Transduction Pathways ◽  
Transduction Pathway ◽  
Cell Functions

Background: During aging and in age-associated disorders, such as Alzheimer's Disease (AD), learning abilities decline. Probably, disturbances in signal transduction in brain cells underlie the cognitive decline. The phosphorylation/dephosphorylation imbalance occurring in degenerating neurons was recently related to abnormal activity of one or more signal transduction pathways. AD is known to be associated with altered neuronal Ca<sup>2+</sup> homeostasis, as Ca<sup>2+</sup> accumulates in affected neurons leading to functional impairment. It is becoming more and more evident the involvement of signal transduction pathways acting upon Ca<sup>2+</sup> metabolism and phosphorylation regulation of proteins. A growing interest raised around the role of signal transduction systems in a number of human diseases including neurodegenerative diseases, with special regard to the systems related to the phosphoinositide (PI) pathway and AD. The PI signal transduction pathway plays a crucial role, being involved in a variety of cell functions, such as hormone secretion, neurotransmitter signal transduction, cell growth, membrane trafficking, ion channel activity, cytoskeleton regulation, cell cycle control, apoptosis, cell and tissue polarity, and contributes to regulate the Ca<sup>2+</sup> levels in the nervous tissue. Conclusion: A number of observations indicated that PI-specific phospholipase C (PLC) enzymes might be involved in the alteration of neurotransmission. To understand the role and the timing of action of the signalling pathways recruited during the brain morphology changes during the AD progression might help to elucidate the aetiopathogenesis of the disease, paving the way to prognosis refinement and/or novel molecular therapeutic strategies.

ras-induced neuronal differentiation of PC12 cells: possible involvement of fos and jun

1989 ◽  
Vol 9 (8) ◽  
pp. 3174-3183
Author(s):  
P Sassone-Corsi ◽  
C J Der ◽  
I M Verma
Keyword(s):  
Signal Transduction ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Transcriptional Activation ◽  
Signal Transduction Pathway ◽  
Cellular Transformation ◽  
Sympathetic Neuron ◽  
Binding Activity ◽  
Ras Protein ◽  
Dna Binding Activity

Rat pheochromocytoma PC12 cells differentiate to sympathetic neuron-like cells upon treatment with nerve growth factor (NGF). The ras and src transforming proteins also induce PC12 neuronal differentiation and are likely to involve the protein kinase C signal transduction pathway. Using a number of ras mutants, we have established that the domains of oncogenic ras protein responsible for PC12 differentiation overlap those required for cellular transformation. All of the ras mutants that induced neuronal differentiation also activated c-fos transcription through the dyad symmetry element (DSE). Transforming ras protein activated an intracellular signal pathway, which led to the induction of 12-O-tetradecanoyl phorbol-13-acetate-responsive elements; activation was enhanced by coexpression of the proto-oncogene jun (encoding AP-1) and was further augmented by fos. Nuclear extracts from ras-infected PC12 cells showed an increased AP-1 DNA-binding activity. Transcriptional activation by ras was independent of the cyclic AMP-dependent pathway of signal transduction. We propose a possible involvement of fos and jun in ras-induced differentiation.

Dysregulated Prefrontal Cortical RhoA Signal Transduction in Bipolar Disorder with Psychosis: New Implications for Disease Pathophysiology

2019 ◽  
Vol 30 (1) ◽  
pp. 59-71
Author(s):  
Bailey A Kermath ◽  
Amanda M Vanderplow ◽  
Michael E Cahill
Keyword(s):  
Signal Transduction ◽  
Bipolar Disorder ◽  
Signal Transduction Pathway ◽  
Signal Transduction Pathways ◽  
Cellular Functions ◽  
Protein Activity ◽  
Cortical Function ◽  
Prefrontal Cortical ◽  
Dorsolateral Prefrontal ◽  
Key Factor

Abstract While research has identified alterations in dorsolateral prefrontal cortical function as a key factor to the etiology of bipolar disorder, few studies have uncovered robust changes in protein signal transduction pathways in this disorder. Given the direct relevance of protein-based expressional alterations to cellular functions and because many of the key regulatory mechanisms for the disease pathogenesis likely include alterations in protein activity rather than changes in expression alone, the identification of alterations in discrete signal transduction pathways in bipolar disorder would have broad implications for understanding the disease pathophysiology. As prior microarray data point to a previously unrecognized involvement of the RhoA network in bipolar disorder, here we investigate the protein expression and activity of key components of a RhoA signal transduction pathway in dorsolateral prefrontal cortical homogenates from subjects with bipolar disorder. The results of this investigation implicate overactivation of prefrontal cortical RhoA signaling in specific subtypes of bipolar disorder. The specificity of these findings is demonstrated by a lack of comparable changes in schizophrenia; however, our findings do identify convergence between both disorders at the level of activity-mediated actin cytoskeletal regulation. These findings have implications for understanding the altered cortical synaptic connectivity of bipolar disorder.

Phytochrome signal-transduction: characterization of pathways and isolation of mutants

1995 ◽  
Vol 350 (1331) ◽  
pp. 67-74 ◽  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Red Light ◽  
Signal Transduction Pathway ◽  
Regulatory Elements ◽  
Signal Transduction Pathways ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Regulated Gene Expression ◽  
Dependent Pathway

The study of phytochrome signalling has yielded a wealth of data describing both the perception of light by the receptor, and the terminal steps in phytochrome-regulated gene expression by a number of transcription factors. We are now focusing on establishing the intervening steps linking phytochrome photoactivation to gene expression, and the regulation and interactions of these signalling pathways. Recent work has utilized both a pharmacological approach in phototrophic soybean suspension cultures and microinjection techniques in tomato to establish three distinct phytochrome signal-transduction pathways: (i) a calcium-dependent pathway that regulates the expression of genes encoding the chlorophyll a/b binding protein ( CAB ) and other components of photosystem II; (ii) a cGMP-dependent pathway that regulates the expression of the gene encoding chalcone synthase ( CHS ) and the production of anthocyanin pigments; and (iii) a pathway dependent upon both calcium and cGMP that regulates the expression of genes encoding components of photosystem I and is necessary for the production of mature chloroplasts. To study the components and the regulation of phytochrome signal-transduction pathways, mutants with altered photomorphogenic responses have been isolated by a number of laboratories. However, with several possible exceptions, little real progress has been made towards the isolation of mutants in positive regulatory elements of the phytochrome signal-transduction pathway. We have characterized a novel phytochrome A (phyA)-mediated far-red light (FR) response in Arabidopsis seedlings which we are currently using to screen for specific phyA signal-transduction mutants.

scholarly journals The β-Arrestin-Like Protein Rim8 Is Hyperphosphorylated and Complexes with Rim21 and Rim101 To Promote Adaptation to Neutral-Alkaline pH

2012 ◽  
Vol 11 (5) ◽  
pp. 683-693 ◽  
Author(s):  
Jonathan Gomez-Raja ◽  
Dana A. Davis
Keyword(s):  
Signal Transduction ◽  
Transcription Factor ◽  
G Protein ◽  
Signal Transduction Pathway ◽  
Multivesicular Bodies ◽  
Ph Sensing ◽  
Content Type ◽  
Protein Levels ◽  
G Protein Coupled

ABSTRACTβ-Arrestin proteins are critical for G-protein-coupled receptor desensitization and turnover. However, β-arrestins have recently been shown to play direct roles in nonheterotrimeric G-protein signal transduction. TheCandida albicansβ-arrestin-like protein Rim8 is required for activation of the Rim101 pH-sensing pathway and for pathogenesis. We have found thatC. albicansRim8 is posttranslationally modified by phosphorylation and specific phosphorylation states are associated with activation of the pH-sensing pathway. Rim8 associated with both the receptor Rim21 and the transcription factor Rim101, suggesting that Rim8 bridges the signaling and activation steps of the pathway. Finally, upon activation of the Rim101 transcription factor,C. albicansRim8 was transcriptionally repressed and Rim8 protein levels were rapidly reduced. Our studies suggest that Rim8 is taken up into multivesicular bodies and degraded within the vacuole. In total, our results reveal a novel mechanism for tightly regulating the activity of a signal transduction pathway. Although the role of β-arrestin proteins in mammalian signal transduction pathways has been demonstrated, relatively little is known about how β-arrestins contribute to signal transduction. Our analyses provide some insights into potential roles.

scholarly journals ras-induced neuronal differentiation of PC12 cells: possible involvement of fos and jun.

1989 ◽  
Vol 9 (8) ◽  
pp. 3174-3183 ◽  
Author(s):  
P Sassone-Corsi ◽  
C J Der ◽  
I M Verma
Keyword(s):  
Signal Transduction ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Transcriptional Activation ◽  
Signal Transduction Pathway ◽  
Cellular Transformation ◽  
Sympathetic Neuron ◽  
Binding Activity ◽  
Ras Protein ◽  
Dna Binding Activity

Rat pheochromocytoma PC12 cells differentiate to sympathetic neuron-like cells upon treatment with nerve growth factor (NGF). The ras and src transforming proteins also induce PC12 neuronal differentiation and are likely to involve the protein kinase C signal transduction pathway. Using a number of ras mutants, we have established that the domains of oncogenic ras protein responsible for PC12 differentiation overlap those required for cellular transformation. All of the ras mutants that induced neuronal differentiation also activated c-fos transcription through the dyad symmetry element (DSE). Transforming ras protein activated an intracellular signal pathway, which led to the induction of 12-O-tetradecanoyl phorbol-13-acetate-responsive elements; activation was enhanced by coexpression of the proto-oncogene jun (encoding AP-1) and was further augmented by fos. Nuclear extracts from ras-infected PC12 cells showed an increased AP-1 DNA-binding activity. Transcriptional activation by ras was independent of the cyclic AMP-dependent pathway of signal transduction. We propose a possible involvement of fos and jun in ras-induced differentiation.

scholarly journals Divergent Regulatory Pathways Control A and S Motility in Myxococcus xanthus through FrzE, a CheA-CheY Fusion Protein

2005 ◽  
Vol 187 (5) ◽  
pp. 1716-1723 ◽  
Author(s):  
Yinuo Li ◽  
Víctor H. Bustamante ◽  
Renate Lux ◽  
David Zusman ◽  
Wenyuan Shi
Keyword(s):  
Signal Transduction ◽  
Fusion Protein ◽  
Myxococcus Xanthus ◽  
Point Mutations ◽  
Cell Movement ◽  
Signal Transduction Pathway ◽  
Enteric Bacteria ◽  
Gliding Motility ◽  
Regulatory Pathways

ABSTRACT Myxococcus xanthus moves on solid surfaces by using two gliding motility systems, A motility for individual-cell movement and S motility for coordinated group movements. The frz genes encode chemotaxis homologues that control the cellular reversal frequency of both motility systems. One of the components of the core Frz signal transduction pathway, FrzE, is homologous to both CheA and CheY from the enteric bacteria and is therefore a novel CheA-CheY fusion protein. In this study, we investigated the role of this fusion protein, in particular, the CheY domain (FrzECheY). FrzECheY retains all of the highly conserved residues of the CheY superfamily of response regulators, including Asp709, analogous to phosphoaccepting Asp57 of Escherichia coli CheY. While in-frame deletion of the entire frzE gene caused both motility systems to show a hyporeversal phenotype, in-frame deletion of the FrzECheY domain resulted in divergent phenotypes for the two motility systems: hyperreversals of the A-motility system and hyporeversals of the S-motility system. To further investigate the role of FrzECheY in A and S motility, point mutations were constructed such that the putative phosphoaccepting residue, Asp709, was changed from D to A (and was therefore never subject to phosphorylation) or E (possibly mimicking constitutive phosphorylation). The D709A mutant showed hyperreversals for both motilities, while the D709E mutant showed hyperreversals for A motility and hyporeversal for S motility. These results show that the FrzECheY domain plays a critical signaling role in coordinating A and S motility. On the basis of the phenotypic analyses of the frzE mutants generated in this study, a model is proposed for the divergent signal transduction through FrzE in controlling and coordinating A and S motility in M. xanthus.

The PI3 kinase, p38 SAP kinase, and NF-κB signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte–derived dendritic cells

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 1039-1046 ◽  
Author(s):  
Kirit M. Ardeshna ◽  
Arnold R. Pizzey ◽  
Stephen Devereux ◽  
Asim Khwaja
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Human Monocyte ◽  
Functional Change ◽  
Pi3 Kinase ◽  
Signal Transduction Pathways ◽  
Hla Dr ◽  
Extracellular Signal ◽  
Induced Changes

Abstract As a dendritic cell (DC) matures, it becomes more potent as an antigen-presenting cell. This functional change is accompanied by a change in DC immunophenotype. The signal transduction events underlying this process are poorly characterized. In this study, we have investigated the signal transduction pathways involved in the lipopolysaccharide (LPS)-induced maturation of human monocyte–derived DCs (MoDCs) in vitro. We show that exposure of immature MoDCs to LPS activates the p38 stress-activated protein kinase (p38SAPK), extracellular signal–regulated protein kinase (ERK), phosphoinositide 3-OH kinase (PI3 kinase)/Akt, and nuclear factor (NF)-κB pathways. Studies using inhibitors demonstrate that PI3 kinase/Akt but not the other pathways are important in maintaining survival of LPS-stimulated MoDCs. Inhibiting p38SAPK prevented activation of the transcription factors ATF-2 and CREB and significantly reduced the LPS-induced up-regulation of CD80, CD83, and CD86, but did not have any significant effect on the LPS-induced changes in macropinocytosis or HLA-DR, CD40, and CD1a expression. Inhibiting the NF-κB pathway significantly reduced the LPS-induced up-regulation of HLA-DR as well as CD80, CD83, and CD86. Inhibiting the p38SAPK and NF-κB pathways simultaneously had variable effects depending on the cell surface marker studied. It thus appears that different aspects of LPS-induced MoDC maturation are regulated by different and sometimes overlapping pathways.

Sign in / Sign up

Export Citation Format

Share Document