The neuropeptide PACAP38 induces dendritic spine remodeling through ADAM10-N-cadherin signaling pathway

Fabrizio Gardoni, Claudia Saraceno, Matteo Malinverno, Elena Marcello, Chiara Verpelli, Carlo Sala, Monica Di Luca

Research output: Contribution to journalArticle

Abstract

The neuropeptide pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) has been implicated in the induction of synaptic plasticity at the excitatory glutamatergic synapse. In particular, recent studies have shown that it is involved in the regulation of Nmethyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activation. Here we demonstrate the effect of PACAP38 on the modulation of dendritic spine morphology through a disintegrin and metalloproteinase 10 (ADAM10)-N-cadherin-AMPA receptor signaling pathway. Treatment of primary hippocampal neurons with PACAP38 induced an accumulation of ADAM10 at the postsynaptic membrane. This event led to a significant decrease of dendritic spine head width and to a concomitant reduction of GluR1 colocalization with postsynaptic markers. The PACAP38-induced effect on dendritic spine head width was prevented by either treatment with the ADAM10-specific inhibitor or transfection of a cleavage-defective N-cadherin construct mutated in the ADAM10 cleavage site. Overall, our findings reveal that PACAP38 is involved in the modulation of dendritic spine morphology in hippocampal neurons, and assign to the ADAM10-N-cadherin signaling pathway a crucial role in this modification of the excitatory glutamatergic synapse.

Original languageEnglish
Pages (from-to)1401-1406
Number of pages6
JournalJournal of Cell Science
Volume125
Issue number6
DOIs
Publication statusPublished - Mar 15 2012

Keywords

  • ADAM10
  • PACAP38
  • Spine morphology

ASJC Scopus subject areas

  • Cell Biology

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