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

Ana del Puerto, Juan Ignacio Díaz-Hernández, Mónica Tapia, Rosa Gomez-Villafuertes, María José Benitez, Jin Zhang, María Teresa Miras-Portugal, Francisco Wandosell, Miguel Díaz-Hernández, Juan José Garrido

Research output: Contribution to journalArticle

Abstract

In 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.

Original languageEnglish (US)
Pages (from-to)176-188
Number of pages13
JournalJournal of Cell Science
Volume125
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Purinergic P2X7 Receptors
Purinergic Receptors
Adenylyl Cyclases
Adenosine Diphosphate
Adenosine Triphosphate
Purinergic P2Y1 Receptors
Neurons
Axons
Purines
Neural Stem Cells
Biosensing Techniques
Phosphatidylinositol 3-Kinases
Synaptic Transmission
Neuroglia
Small Interfering RNA
Plasmids
Inflammation
Brain

Keywords

  • Adenylate cyclase
  • Axon elongation
  • Purinergic receptor

ASJC Scopus subject areas

  • Cell Biology

Cite this

del Puerto, A., Díaz-Hernández, J. I., Tapia, M., Gomez-Villafuertes, R., Benitez, M. J., Zhang, J., ... Garrido, J. J. (2012). Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation. Journal of Cell Science, 125(1), 176-188. https://doi.org/10.1242/jcs.091736

Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation. / del Puerto, Ana; Díaz-Hernández, Juan Ignacio; Tapia, Mónica; Gomez-Villafuertes, Rosa; Benitez, María José; Zhang, Jin; Miras-Portugal, María Teresa; Wandosell, Francisco; Díaz-Hernández, Miguel; Garrido, Juan José.

In: Journal of Cell Science, Vol. 125, No. 1, 01.01.2012, p. 176-188.

Research output: Contribution to journalArticle

del Puerto, A, Díaz-Hernández, JI, Tapia, M, Gomez-Villafuertes, R, Benitez, MJ, Zhang, J, Miras-Portugal, MT, Wandosell, F, Díaz-Hernández, M & Garrido, JJ 2012, 'Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation', Journal of Cell Science, vol. 125, no. 1, pp. 176-188. https://doi.org/10.1242/jcs.091736
del Puerto A, Díaz-Hernández JI, Tapia M, Gomez-Villafuertes R, Benitez MJ, Zhang J et al. Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation. Journal of Cell Science. 2012 Jan 1;125(1):176-188. https://doi.org/10.1242/jcs.091736
del Puerto, Ana ; Díaz-Hernández, Juan Ignacio ; Tapia, Mónica ; Gomez-Villafuertes, Rosa ; Benitez, María José ; Zhang, Jin ; Miras-Portugal, María Teresa ; Wandosell, Francisco ; Díaz-Hernández, Miguel ; Garrido, Juan José. / Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation. In: Journal of Cell Science. 2012 ; Vol. 125, No. 1. pp. 176-188.
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AU - Tapia, Mónica

AU - Gomez-Villafuertes, Rosa

AU - Benitez, María José

AU - Zhang, Jin

AU - Miras-Portugal, María Teresa

AU - Wandosell, Francisco

AU - Díaz-Hernández, Miguel

AU - Garrido, Juan José

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N2 - In 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.

AB - In 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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