Tissue-nonspecific alkaline phosphatase promotes axonal growth of hippocampal neurons

Diez-Zaera, María; Díaz‐Hernandéz, Juan Ignacio; Hernández-Álvarez, Elena; Zimmermann, Herbert; Dı́az-Hernández, Miguel; Miras‐Portugal, M. Teresa

doi:10.1091/mbc.e10-09-0740

Cited by 91 publications

(83 citation statements)

References 48 publications

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“…In this sense, the different ectonucleotidase families that modify the number of phosphates in adenine nucleotides could be important regulators (Langer et al, 2008). For example, expression in cultured neurons of tissue non-specific alkaline phosphatase (TNAP), which reduces extracellular ATP levels, improves axonal growth (Diez-Zaera et al, 2011). Our results suggest that axon elongation is regulated through the coordination of the ionotropic ATP-gated P2X7 receptor and ADP-activated P2Y receptors.…”

Section: Discussionmentioning

confidence: 83%

Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation

Puerto

Díaz‐Hernandéz

Tapia

et al. 2012

Journal of Cell Science

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SummaryIn adult brains, ionotropic or metabotropic purinergic receptors are widely expressed in neurons and glial cells. They play an essential role in inflammation and neurotransmission in response to purines secreted to the extracellular medium. Recent studies have demonstrated a role for purinergic receptors in proliferation and differentiation of neural stem cells although little is known about their role in regulating the initial neuronal development and axon elongation. The objective of our study was to investigate the role of some different types of purinergic receptors, P2Y1, P2Y13 and P2X7, which are activated by ADP or ATP. To study the role and crosstalk of P2Y1, P2Y13 and P2X7 purinergic receptors in axonal elongation, we treated neurons with specific agonists and antagonists, and we nucleofected neurons with expression or shRNA plasmids. ADP and P2Y1-GFP expression improved axonal elongation; conversely, P2Y13 and ATP-gated P2X7 receptors halted axonal elongation. Signaling through each of these receptor types was coordinated by adenylate cyclase 5. In neurons nucleofected with a cAMP FRET biosensor (ICUE3), addition of ADP or Blue Brilliant G, a P2X7 antagonist, increased cAMP levels in the distal region of the axon. Adenylate cyclase 5 inhibition or suppression impaired these cAMP increments. In conclusion, our results demonstrate a crosstalk between two metabotropic and one ionotropic purinergic receptor that regulates cAMP levels through adenylate cyclase 5 and modulates axonal elongation triggered by neurotropic factors and the PI3K-Akt-GSK3 pathway.

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Section: Discussionmentioning

confidence: 83%

Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation

Puerto

Díaz‐Hernandéz

Tapia

et al. 2012

Journal of Cell Science

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“…Furthermore, inhibiting the P2X7 receptor reduced TNAP expression, whereas the addition of AP enhanced P2X7 receptor expression. The results suggested that TNAP, by regulating both ligand availability and protein expression of P2X7 receptors, is important for axonal development [517]. TNAP was also found to be essential for the differentiation of cultured adult neural stem cells into neurons or oligodendrocytes.…”

Section: Downstream Signalingmentioning

confidence: 97%

“…To date, the functional involvement of APs in purinergic signaling has received rather little attention. An involvement in purinergic signaling has been implicated for TNAP in NG108-15 neuronal cells [515], in human airways [464,516], in bone remodeling [24], and in the control of axon outgrowth in cultured hippocampal neurons [517].…”

Section: Substrates and Catalytic Propertiesmentioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

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922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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“…P2X7 receptors could also be involved in neuronal development. Both the P2X7 receptor and the ectoenzyme tissuenonspecific alkaline phosphatase are expressed in mouse hippocampal neurons at early stages of differentiation, thereby controlling, in a coordinated way, the elongation of the growth cone (Díez-Zaera et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Purinergic P2X7 Receptors Mediate Cell Death in Mouse Cerebellar Astrocytes in Culture

Salas

Carrasquero

Olivos-Oré

et al. 2013

The Journal of Pharmacology and Experimental Therapeutics

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The brain distribution and functional role of glial P2X7 receptors are broader and more complex than initially anticipated. We characterized P2X7 receptors from cerebellar astrocytes at the molecular, immunocytochemical, biophysical, and cell physiologic levels. Mouse cerebellar astrocytes in culture express mRNA coding for P2X7 receptors, which is translated into P2X7 receptor protein as proven by Western blot analysis and immunocytochemistry. Fura-2 imaging showed cytosolic calcium responses to ATP and the synthetic analog 39-O-(4-benzoyl)benzoyl-ATP (BzATP) exhibited two components, namely an initial transient and metabotropic component followed by a sustained one that depended on extracellular calcium. This latter component, which was absent in astrocytes from P2X7 receptor knockout mice (P2X7 KO), was modulated by extracellular Mg 21, and was sensitive to Brilliant Blue G (BBG) and 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl pyridine (A438079) antagonism. BzATP also elicited inwardly directed nondesensitizing whole-cell ionic currents that were reduced by extracellular Mg 21 and P2X7 antagonists (BBG and calmidazolium). In contrast to that previously reported in rat cerebellar astrocytes, sustained BzATP application induced a gradual increase in membrane permeability to large cations, such as N-methyl-D-glucamine and 4-[3-methyl-2(3H)-benzoxazolylidene)-methyl]-1-[3-(triethylammonio)propyl]diiodide, which ultimately led to the death of mouse astrocytes. Cerebellar astrocyte cell death was prevented by BBG but not by calmidazolium, removal of extracellular calcium, or treatment with the caspase-3 inhibitor, benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone, thus suggesting a necrotictype mechanism of cell death. Since this cellular response was not observed in astrocytes from P2X7 KO mice, this study suggests that stimulation of P2X7 receptor may convey a cell death signal to cerebellar astrocytes in a species-specific manner.

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Tissue-nonspecific alkaline phosphatase promotes axonal growth of hippocampal neurons

Abstract: A reduction in extracellular ATP levels by TNAP is essential for the development of neuritic processes by cultured hippocampal neurons. Results demonstrate that TNAP-mediated effects regulate both ligand availability and protein expression of P2X7 receptor in the axonal growth cone.

Cited by 91 publications

References 48 publications

Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation

Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation

Cellular function and molecular structure of ecto-nucleotidases

Purinergic P2X7 Receptors Mediate Cell Death in Mouse Cerebellar Astrocytes in Culture

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