scholarly journals Difference in XTcf-3 dependency accounts for change in response to β-catenin-mediated Wnt signalling in Xenopus blastula

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 2063-2073 ◽  
Author(s):  
Fiona S. Hamilton ◽  
Grant N. Wheeler ◽  
Stefan Hoppler

Wnt signalling functions in many tissues and during different stages of animal development to produce very specific responses. In early Xenopus embryos there is a dramatic change in response to Wnt signalling within only a few hours of development. Wnt signalling in very early embryos leads to a dorsalising response, which establishes the endogenous dorsal axis. Only a few hours later in development, almost the opposite happens: Xwnt-8 functions to pattern the embryonic mesoderm by promoting ventral and lateral mesoderm. The specificity of the response could conceivably be carried out by differential use of different signal transduction pathways, many of which have recently been described. We have found, however, that this dramatic shift in response to Wnt signalling in early Xenopus is not brought about by differential use of distinct signal transduction pathways. In fact β-catenin, a downstream component of the canonical Wnt signal transduction pathway, functions not only in the early dorsalising response but also in the later ventrolateral-promoting response. Interaction of β-catenin with the XTcf-3 transcription factor is required for the early dorsalising activity. In contrast, our experiments suggest that late Wnt signalling in the ventrolateral mesoderm does not require a similar dependency of β-catenin function on XTcf-3. Our results highlight the potential versatility of the canonical Wnt pathway to interact with tissue-specific factors downstream of β-catenin, in order to achieve tissue-specific effects.

2010 ◽  
Vol 44 (4) ◽  
pp. 195-201 ◽  
Author(s):  
Samantha Gardner ◽  
Emmanouil Stavrou ◽  
Patricia E Rischitor ◽  
Elena Faccenda ◽  
Adam J Pawson

The binding of GnRH to its receptor on pituitary gonadotropes leads to the targeting of a diverse array of signalling mediators. These mediators drive multiple signal transduction pathways, which in turn regulate a variety of cellular processes, including the biosynthesis and secretion of the gonadotropins LH and FSH. Advances in our understanding of the mechanisms and signalling pathways that are recruited to regulate gonadotrope function are continually being made. This review will focus on the recent demonstration that key mediators of the canonical Wnt signalling pathway are targeted by GnRH in gonadotropes, and that these may play essential roles in regulating the expression of many of the key players in gonadotrope biology, including the GnRH receptor and the gonadotropins.


2018 ◽  
Vol 15 (4) ◽  
pp. 355-362 ◽  
Author(s):  
Vincenza Rita Lo Vasco

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.


2019 ◽  
Vol 30 (1) ◽  
pp. 59-71
Author(s):  
Bailey A Kermath ◽  
Amanda M Vanderplow ◽  
Michael E Cahill

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.


Cardiology ◽  
2019 ◽  
Vol 145 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Qunying Xi ◽  
Zhihong Liu ◽  
Yunhu  Song ◽  
Huili Gan ◽  
Zhiwei Huang ◽  
...  

Background: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown. Proteomics offers an approach to overview the molecular activities and signal transduction pathways involved in specific disease processes. Objectives: In this study, the expression of proteins in endarterectomized tissues from patients with CTEPH was investigated in a novel strategy to explore the pathophysiology of this disease. Methods: We used the iTRAQ (isobaric tag for relative and absolute quantitation) approach combined with a Thermo Scientific Q Exactive MS analysis to compare the protein profiles in endarterectomized tissues from CTEPH patients and that of the control samples (mixture of cultured human pulmonary artery endothelial cells, human pulmonary artery smooth muscle cells, and human pulmonary fibroblasts). GO and KEGG analyses were performed to understand the functional classification and molecular activities of all the tissue-specific proteins, and the involved signal transduction pathways. Results: Six hundred and seventy-nine tissue-specific proteins were detected. Bioinformatic analysis showed that the major biological processes involving these proteins were: response to wounding, defense response, acute inflammatory response, immune response, complement activation, and blood coagulation. The main pathways involved were: complement and coagulation cascade, systemic lupus erythematosus, extracellular matrix-receptor interaction, cell adhesion molecules, FcεRI signaling, and leukocyte transendothelial migration. Conclusions: The present study revealed that immune and defense response might play an important role in CTEPH.


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.


1995 ◽  
Vol 128 (6) ◽  
pp. 1111-1119 ◽  
Author(s):  
C Rosette ◽  
M Karin

Cell shape changes exert specific effects on gene expression. It has been speculated that the cytoskeleton is responsible for converting changes in the cytoarchitecture to effects on gene transcription. However, the signal transduction pathways responsible for cytoskeletal-nuclear communication remained unknown. We now provide evidence that a variety of agents and conditions that depolymerize microtubules activate the sequence-specific transcription factor NF-kappa B and induce NF kappa B-dependent gene expression. These effects are caused by depolymerization of microtubule because they are blocked by the microtubule-stabilizing agent taxol. In nonstimulated cells, the majority of NF-kappa B resides in the cytosplasm as a complex with its inhibitor I kappa B. Upon cell stimulation, NF-kappa B translocates to the nucleus with concomitant degradation of I kappa B. We show that cold-induced depolymerization of microtubules also leads to I kappa B degradation and activation of NF-kappa B. However, the activated factor remains in the cytoplasm and translocates to the nucleus only upon warming to 37 degrees C, thus revealing two distinct steps in NF-kappa B activation. These findings establish a new role for NF-kappa B in sensing changes in the state of the cytoskeleton and converting them to changes in gene activity.


1998 ◽  
Vol 329 (2) ◽  
pp. 209-223 ◽  
Author(s):  
C. Trevor DALE

The Wnt genes encode a large family of secreted polypeptides that mediate cell-cell communication in diverse developmental processes. The loss or inappropriate activation of Wnt expression has been shown to alter cell fate, morphogenesis and mitogenesis. Recent progress has identified Wnt receptors and components of an intracellular signalling pathway that mediate Wnt-dependent transcription. This review will highlight this ‘core’ Wnt signal-transduction pathway, but also aims to reveal the potential diversity of Wnt signalling targets. Particular attention will be paid to the overlap between developmental biology and oncogenesis, since recent progress shows Wnt signalling forms a paradigm for an interdisciplinary approach.


Genetics ◽  
1999 ◽  
Vol 153 (3) ◽  
pp. 1219-1231
Author(s):  
Paula M Alepuz ◽  
Dina Matheos ◽  
Kyle W Cunningham ◽  
Francisco Estruch

Abstract In eukaryotes, control of transcription by extracellular signals involves the translocation to the nucleus of at least one component of the signal transduction pathway. Transport through the nuclear envelope requires the activity of an import or export receptor that interacts with the small GTPase Ran. We have cloned the MSN5 gene of the yeast Saccharomyces cerevisiae that is postulated to encode one of these receptors. Msn5p belongs to a family of proteins with a conserved N-terminal sequence that acts as a RanGTP-binding domain. The results presented here provide genetic data supporting Msn5p involvement in several different signal transduction pathways. All of these pathways include changes in gene expression, and regulated nucleocytoplasmic redistribution of a component in response to external conditions has already been described in some of them. We have cloned MSN5 following two different strategies. Msn5p was constitutively localized in the nucleus. Phenotypic analysis of the msn5 mutant demonstrated that this protein participates in processes such as catabolite repression, calcium signaling, mating, and cell proliferation, as well as being involved in previously characterized phosphate utilization. Therefore, Msn5p could be a receptor for several proteins involved in different signaling pathways.


2021 ◽  
Author(s):  
CHONG CHEN ◽  
Xuejing Wang ◽  
Ying Wang ◽  
Liangfei Tian ◽  
Jinxuan Cao

The maintenance of an orderly and controllable multicellular society depends on the communication and signal regulation among various types of biological cells. How to replicate complicate signal transduction pathways in...


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