MOLECULAR MECHANISMS REGULATING SPINE REMODELLING [Tesi di dottorato]
Università degli Studi di Milano, 2010-12-15

N-Cadherin plays an important role during dendrite arborisation, axon guidance and synaptogenesys. In particular, at synaptic sites, it is required for activity-dependent synaptic plasticity and dendritic spine remodeling. Recent studies have shown that N-Cadherin can be cleaved by the metalloproteinase ADAM10. Here we demonstrate that modulating ADAM10 localization and activity at synaptic sites regulates its processing of N-Cadherin. This indices modification of dendritic spines morphology and of composition and function of AMPA receptors. In particular, inhibition of ADAM10 synaptic localization and activity leads to an accumulation of the full-length form of N-cadherin, to an increase in spine head width and to modifications of number and function of glutamate receptors of AMPA-type, both in vitro and in vivo. Conversely, the stimulation of ADAM10 activity towards N-Cadherin reduces dendritic spine size and AMPA receptor localization at post-synaptic sites

diritti: info:eu-repo/semantics/openAccess
Coordinatore: Guido Franceschini ; Tutor: Monica Diluca
DILUCA, MONICA MARIA GRAZIA
FRANCESCHINI, GUIDO
Settore BIO/14 - - Farmacologia


Tesi di dottorato. | Lingua: Inglese. | Paese: | BID: TD16000177