title: ATP Released by Injured Neurons Activates Schwann Cells.
abstract: Injured nerve terminals of neuromuscular junctions (NMJs) can regenerate. This remarkable and complex response is governed by molecular signals that are exchanged among the cellular components of this synapse: motor axon nerve terminal (MAT), perisynaptic Schwann cells (PSCs), and muscle fiber. The nature of signals that govern MAT regeneration is ill-known. In the present study the spider toxin α-latrotoxin has been used as tool to investigate the mechanisms underlying peripheral neuroregeneration. Indeed this neurotoxin induces an acute, specific, localized and fully reversible damage of the presynaptic nerve terminal, and its action mimics the cascade of events that leads to nerve terminal degeneration in injured patients and in many neurodegenerative conditions. Here we provide evidence of an early release by degenerating neurons of adenosine triphosphate as alarm messenger, that contributes to the activation of a series of intracellular pathways within Schwann cells that are crucial for nerve regeneration: Ca(2+), cAMP, ERK1/2, and CREB. These results contribute to define the cross-talk taking place among degenerating nerve terminals and PSCs, involved in the functional recovery of the NMJ.
authors.affiliation: Department of Biomedical Sciences, University of Padova Padua, Italy.
authors.forename: Samuele
authors.initials: S
authors.lastname: Negro
authors.affiliation: Department of Biomedical Sciences, University of Padova Padua, Italy.
authors.forename: Elisanna
authors.initials: E
authors.lastname: Bergamin
authors.affiliation: Department of Biomedical Sciences, University of Padova Padua, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Rodella
authors.affiliation: Department of Biomedical Sciences, University of Padova Padua, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Duregotti
authors.affiliation: Department of Biomedical Sciences, University of Padova Padua, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Scorzeto
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute Amsterdam, Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: Jalink
authors.affiliation: Department of Biomedical Sciences, University of PadovaPadua, Italy; National Research Council, Institute of NeurosciencePadua, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
authors.affiliation: Department of Biomedical Sciences, University of Padova Padua, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Rigoni
keywords: ATP; CREB; ERK 1/2; Schwann cells; apyrase; cAMP; calcium; primary neurons