Extracellular nucleotides and nucleosides as signalling molecules

Extracellular nucleotides are ubiquitous signalling molecules which modulate distinct physiological and pathological processes. Nucleotide concentrations in the extracellular space are strictly regulated by cell surface enzymes, called ectonucleotidases, which hydrolyze nucleotides to the respective nucleosides. Recent studies suggest that ectonucleotidases play a significant role in inflammation by adjusting the balance between ATP, a widely distributed proinflammatory danger signal, and the anti-inflammatory mediator adenosine. There is increasing evidence for a central role of adenosine in alloantigen-mediated diseases such as solid organ graft rejection and acute graft-versus-host disease (GvHD). Solid organ and hematopoietic cell transplantation are established treatment modalities for a broad spectrum of benign and malignant diseases. Immunological complications based on the recognition of nonself-antigens between donor and recipient like transplant rejection and GvHD are still major challenges which limit the long-term success of transplantation. Studies in the past two decades indicate that purinergic signalling influences the severity of alloimmune responses. This paper focuses on the impact of ectonucleotidases, in particular, NTPDase1/CD39 and ecto-5′-nucleotidase/CD73, on allograft rejection, acute GvHD, and graft-versus-leukemia effect, and on possible clinical implications for the modulation of purinergic signalling after transplantation.

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Effects of extracellular nucleotides and nucleosides on prostate carcinoma cells

British Journal of Pharmacology ◽

10.1038/sj.bjp.0703833 ◽

2001 ◽

Vol 132 (2) ◽

pp. 536-546 ◽

Cited By ~ 61

Author(s):

Rodolphe Janssens ◽

Jean-Marie Boeynaems

Keyword(s):

Prostate Carcinoma ◽

Carcinoma Cells ◽

Extracellular Nucleotides ◽

Nucleotides And Nucleosides

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Intertwining extracellular nucleotides and their receptors with Ca 2+ in determining adult neural stem cell survival, proliferation and final fate

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2015.0433 ◽

2016 ◽

Vol 371 (1700) ◽

pp. 20150433 ◽

Cited By ~ 7

Author(s):

Davide Lecca ◽

Marta Fumagalli ◽

Stefania Ceruti ◽

Maria P. Abbracchio

Keyword(s):

Spinal Cord ◽

Adult Brain ◽

Extracellular Nucleotides ◽

Purinergic Signalling ◽

Spinal Cord Development ◽

Calcium Dependent ◽

Signalling Molecules ◽

Adult Nscs ◽

Parenchymal Injury ◽

Brain And Spinal Cord

In the central nervous system (CNS), during both brain and spinal cord development, purinergic and pyrimidinergic signalling molecules (ATP, UTP and adenosine) act synergistically with peptidic growth factors in regulating the synchronized proliferation and final specification of multipotent neural stem cells (NSCs) to neurons, astrocytes or oligodendrocytes, the myelin-forming cells. Some NSCs still persist throughout adulthood in both specific ‘neurogenic’ areas and in brain and spinal cord parenchyma, retaining the potentiality to generate all the three main types of adult CNS cells. Once CNS anatomical structures are defined, purinergic molecules participate in calcium-dependent neuron-to-glia communication and also control the behaviour of adult NSCs. After development, some purinergic mechanisms are silenced, but can be resumed after injury, suggesting a role for purinergic signalling in regeneration and self-repair also via the reactivation of adult NSCs. In this respect, at least three different types of adult NSCs participate in the response of the adult brain and spinal cord to insults: stem-like cells residing in classical neurogenic niches, in particular, in the ventricular–subventricular zone (V-SVZ), parenchymal oligodendrocyte precursor cells (OPCs, also known as NG2-glia) and parenchymal injury-activated astrocytes (reactive astrocytes). Here, we shall review and discuss the purinergic regulation of these three main adult NSCs, with particular focus on how and to what extent modulation of intracellular calcium levels by purinoceptors is mandatory to determine their survival, proliferation and final fate. This article is part of the themed issue ‘Evolution brings Ca 2+ and ATP together to control life and death’.

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Enzymes involved in metabolism of extracellular nucleotides and nucleosides: Functional implications and measurement of activities

Critical Reviews in Biochemistry and Molecular Biology ◽

10.3109/10409238.2014.953627 ◽

2014 ◽

Vol 49 (6) ◽

pp. 473-497 ◽

Cited By ~ 143

Author(s):

Gennady G. Yegutkin

Keyword(s):

Extracellular Nucleotides ◽

Nucleotides And Nucleosides ◽

Functional Implications

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Caveolin-1, galectin-3 and lipid raft domains in cancer cell signalling

Essays in Biochemistry ◽

10.1042/bse0570189 ◽

2015 ◽

Vol 57 ◽

pp. 189-201 ◽

Cited By ~ 13

Author(s):

Jay Shankar ◽

Cecile Boscher ◽

Ivan R. Nabi

Keyword(s):

Plasma Membrane ◽

Lipid Rafts ◽

Cancer Cell ◽

Cellular Response ◽

Spatial Organization ◽

Essential Feature ◽

Cell Signalling ◽

Coated Pits ◽

Signalling Molecules ◽

Raft Domains

Spatial organization of the plasma membrane is an essential feature of the cellular response to external stimuli. Receptor organization at the cell surface mediates transmission of extracellular stimuli to intracellular signalling molecules and effectors that impact various cellular processes including cell differentiation, metabolism, growth, migration and apoptosis. Membrane domains include morphologically distinct plasma membrane invaginations such as clathrin-coated pits and caveolae, but also less well-defined domains such as lipid rafts and the galectin lattice. In the present chapter, we will discuss interaction between caveolae, lipid rafts and the galectin lattice in the control of cancer cell signalling.

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Plant peptide hormone signalling

Essays in Biochemistry ◽

10.1042/bse0580115 ◽

2015 ◽

Vol 58 ◽

pp. 115-131 ◽

Cited By ~ 17

Author(s):

Ayane Motomitsu ◽

Shinichiro Sawa ◽

Takashi Ishida

Keyword(s):

Communication Systems ◽

Cell Communication ◽

Peptide Hormone ◽

Peptide Hormones ◽

Target Cells ◽

Signalling Molecules ◽

Receptor Complexes ◽

Environmental Responses ◽

Plant Life Cycle ◽

Multicellular Organisms

The ligand–receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone–receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions.

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