In:
Journal of Cell Science, The Company of Biologists
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 NMDA and AMPA receptor activation. Here we demonstrate the effect of PACAP38 on the modulation of dendritic spine morphology through ADAM10/N-Cadherin/AMPA receptor signaling pathway. Treatment of primary hippocampal neurons with PACAP38 induces an accumulation of ADAM10 at the postsynaptic membrane. This event leads to a significant decrease of dendritic spine head width and to a concomitant reduction of GluR1 co-localization with postsynaptic markers. PACAP38-induced effect on dendritic spine head width is prevented by either treatment with ADAM10 specific inhibitor or transfection of a cleavage-defective N-Cadherin construct, mutated in the ADAM10 cleavage site. Overall, our findings reveal for the first time 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.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2012
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
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