Tissue-nonspecific alkaline phosphatase promotes axonal growth of hippocampal neurons

  • Axonal growth is essential for establishing neuronal circuits during brain development and for regenerative processes in the adult brain. Unfortunately, the extracellular signals controlling axonal growth are poorly understood. Here we report that a reduction in extracellular ATP levels by tissue-nonspecific alkaline phosphatase (TNAP) is essential for the development of neuritic processes by cultured hippocampal neurons. Selective blockade of TNAP activity with levamisole or specific TNAP knockdown with short hairpin RNA interference inhibited the growth and branching of principal axons, whereas addition of alkaline phosphatase (ALP) promoted axonal growth. Neither activation nor inhibition of adenosine receptors affected the axonal growth, excluding the contribution of extracellular adenosine as a potential hydrolysis product of extracellular ATP to the TNAP-mediated effects. TNAP was colocalized at axonal growth cones with ionotropic ATP receptors (P2X7 receptor), whose activation inhibited axonal growth. Additional analyses suggested a close functional interrelation of TNAP and P2X7 receptors whereby TNAP prevents P2X7 receptor activation by hydrolyzing ATP in the immediate environment of the receptor. Furthermore inhibition of P2X7 receptor reduced TNAP expression, whereas addition of ALP enhanced P2X7 receptor expression. Our results demonstrate that TNAP, regulating both ligand availability and protein expression of P2X7 receptor, is essential for axonal development.

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Metadaten
Author:Maria Díez-Zaera, Juan Ignacio Díaz-Hernández, Elena Hernández-Álvarez, Herbert ZimmermannORCiDGND, Miguel Díaz-Hernández, María Teresa Miras Portugal
URN:urn:nbn:de:hebis:30:3-240907
DOI:https://doi.org/10.1091/mbc.E10-09-0740
ISSN:1939-4586
ISSN:1059-1524
Parent Title (English):Molecular biology of the cell
Publisher:American Society for Cell Biology
Place of publication:Bethesda, Md.
Editor:Kozo Kaibuchi
Document Type:Article
Language:English
Year of Completion:2011
Date of first Publication:2011/02/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2012/05/14
Volume:22
Issue:10
Page Number:11
First Page:1014
Last Page:1024
HeBIS-PPN:311938205
Institutes:Biowissenschaften / Biowissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen