Recent studies have indicated that the serotonin receptor subtype 7 (5-HT7R) plays a crucial role in shaping neuronal morphology during embryonic and early postnatal life. Here we show that pharmacological stimulation of 5-HT7R using a highly selective agonist, LP-211, enhances neurite outgrowth in neuronal primary cultures from the cortex, hippocampus and striatal complex of embryonic mouse brain, through multiple signal transduction pathways. All these signaling systems, involving mTOR, the Rho GTPase Cdc42, Cdk5, and ERK, are known to converge on the reorganization of cytoskeletal proteins that subserve neurite outgrowth. Indeed, our data indicate that neurite elongation stimulated by 5-HT7R is modulated by drugs affecting actin polymerization. In addition, we show, by 2D Western blot analyses, that treatment of neuronal cultures with LP-211 alters the expression profile of cofilin, an actin binding protein involved in microfilaments dynamics. Furthermore, by using microfluidic chambers that physically separate axons from the soma and dendrites, we demonstrate that agonist-dependent activation of 5-HT7R stimulates axonal elongation. Our results identify for the first time several signal transduction pathways, activated by stimulation of 5-HT7R, that converge to promote cytoskeleton reorganization and consequent modulation of axonal elongation. Therefore, the activation of 5-HT7R might represent one of the key elements regulating CNS connectivity and plasticity during development.

Activation of 5-HT7 receptor stimulates neurite elongation through mTOR, Cdc42 and actin filaments dynamics / Speranza, Luisa; Giuliano, T; Volpicelli, Floriana; De Stefano, Me; Lombardi, L; Chambery, A; Lacivita, E; Leopoldo, M; Bellenchi, Gc; di Porzio, U; Crispino, Marianna; PERRONE CAPANO, Carla. - In: FRONTIERS IN BEHAVIORAL NEUROSCIENCE. - ISSN 1662-5153. - 9:(2015), p. 62. [10.3389/fnbeh.2015.00062]

Activation of 5-HT7 receptor stimulates neurite elongation through mTOR, Cdc42 and actin filaments dynamics.

SPERANZA, LUISA;VOLPICELLI, FLORIANA;CRISPINO, MARIANNA
;
PERRONE CAPANO, CARLA
Ultimo
2015

Abstract

Recent studies have indicated that the serotonin receptor subtype 7 (5-HT7R) plays a crucial role in shaping neuronal morphology during embryonic and early postnatal life. Here we show that pharmacological stimulation of 5-HT7R using a highly selective agonist, LP-211, enhances neurite outgrowth in neuronal primary cultures from the cortex, hippocampus and striatal complex of embryonic mouse brain, through multiple signal transduction pathways. All these signaling systems, involving mTOR, the Rho GTPase Cdc42, Cdk5, and ERK, are known to converge on the reorganization of cytoskeletal proteins that subserve neurite outgrowth. Indeed, our data indicate that neurite elongation stimulated by 5-HT7R is modulated by drugs affecting actin polymerization. In addition, we show, by 2D Western blot analyses, that treatment of neuronal cultures with LP-211 alters the expression profile of cofilin, an actin binding protein involved in microfilaments dynamics. Furthermore, by using microfluidic chambers that physically separate axons from the soma and dendrites, we demonstrate that agonist-dependent activation of 5-HT7R stimulates axonal elongation. Our results identify for the first time several signal transduction pathways, activated by stimulation of 5-HT7R, that converge to promote cytoskeleton reorganization and consequent modulation of axonal elongation. Therefore, the activation of 5-HT7R might represent one of the key elements regulating CNS connectivity and plasticity during development.
2015
Activation of 5-HT7 receptor stimulates neurite elongation through mTOR, Cdc42 and actin filaments dynamics / Speranza, Luisa; Giuliano, T; Volpicelli, Floriana; De Stefano, Me; Lombardi, L; Chambery, A; Lacivita, E; Leopoldo, M; Bellenchi, Gc; di Porzio, U; Crispino, Marianna; PERRONE CAPANO, Carla. - In: FRONTIERS IN BEHAVIORAL NEUROSCIENCE. - ISSN 1662-5153. - 9:(2015), p. 62. [10.3389/fnbeh.2015.00062]
File in questo prodotto:
File Dimensione Formato  
Speranza et al 15.pdf

accesso aperto

Descrizione: articolo principale
Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 2.41 MB
Formato Adobe PDF
2.41 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/11588/602001
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 45
  • ???jsp.display-item.citation.isi??? 43
social impact