A major challenge in the neuroscience field is the identification of molecules and pathways that control synaptic plasticity and memory. Dendritic spines play a pivotal role in these processes, as the major sites of excitatory synapses in neuronal communication. Previous studies have shown that the scaffold protein p140Cap localizes into dendritic spines and that its knockdown negatively modulates spine shape in culture. However, so far, there is no information on its in vivo relevance. By using a knock-out mouse model, we here demonstrate that p140Cap is a key element for both learning and synaptic plasticity. Indeed, p140Cap(-/-) mice are impaired in object recognition test, as well as in LTP and in LTD measurements. The in vivo effects of p140Cap loss are presumably attenuated by noncell-autonomous events, since primary neurons obtained from p140Cap(-/-) mice show a strong reduction in number of mushroom spines and abnormal organization of synapse-associated F-actin. These phenotypes are most likely caused by a local reduction of the inhibitory control of RhoA and of cortactin toward the actin-depolymerizing factor cofilin. These events can be controlled by p140Cap through its capability to directly inhibit the activation of Src kinase and by its binding to the scaffold protein Citron-N. Altogether, our results provide new insight into how protein associated with dynamic microtubules may regulate spine actin organization through interaction with postsynaptic density components.

p140Cap regulates memory and synaptic plasticity through Src-mediated and citron-N-mediated actin reorganization.

REPETTO, DANIELE;CAMERA, Paola;MORELLO, Noemi;RUSSO, ISABELLA;CALCAGNO, ELEONORA;BIANCHI, Federico Tommaso;BERTO, GAIA ELENA;GIUSTETTO, Maurizio;DI STEFANO, PAOLA;TURCO, Emilia;DI CUNTO, Ferdinando;DEFILIPPI, Paola
2014-01-01

Abstract

A major challenge in the neuroscience field is the identification of molecules and pathways that control synaptic plasticity and memory. Dendritic spines play a pivotal role in these processes, as the major sites of excitatory synapses in neuronal communication. Previous studies have shown that the scaffold protein p140Cap localizes into dendritic spines and that its knockdown negatively modulates spine shape in culture. However, so far, there is no information on its in vivo relevance. By using a knock-out mouse model, we here demonstrate that p140Cap is a key element for both learning and synaptic plasticity. Indeed, p140Cap(-/-) mice are impaired in object recognition test, as well as in LTP and in LTD measurements. The in vivo effects of p140Cap loss are presumably attenuated by noncell-autonomous events, since primary neurons obtained from p140Cap(-/-) mice show a strong reduction in number of mushroom spines and abnormal organization of synapse-associated F-actin. These phenotypes are most likely caused by a local reduction of the inhibitory control of RhoA and of cortactin toward the actin-depolymerizing factor cofilin. These events can be controlled by p140Cap through its capability to directly inhibit the activation of Src kinase and by its binding to the scaffold protein Citron-N. Altogether, our results provide new insight into how protein associated with dynamic microtubules may regulate spine actin organization through interaction with postsynaptic density components.
2014
34
4
1542
1553
http://www.jneurosci.org/content/34/4/1542.long
Repetto D;Camera P;Melani R;Morello N;Russo I;Calcagno E;Tomasoni R;Bianchi F;Berto G;Giustetto M;Berardi N;Pizzorusso T;Matteoli M;Di Stefano P;Missler M;Turco E;Di Cunto F;Defilippi P
File in questo prodotto:
File Dimensione Formato  
1294827.pdf

Accesso aperto

Tipo di file: PDF EDITORIALE
Dimensione 3.06 MB
Formato Adobe PDF
3.06 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/143017
Citazioni
  • ???jsp.display-item.citation.pmc??? 27
  • Scopus 43
  • ???jsp.display-item.citation.isi??? 39
social impact