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Front Behav Neurosci. 2015 Mar 11;9:62. doi: 10.3389/fnbeh.2015.00062. eCollection 2015.

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

Author information

1
Department of Biology, University of Naples Federico II Naples, Italy ; Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR Naples, Italy.
2
Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR Naples, Italy.
3
Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR Naples, Italy ; Department of Pharmacy, University of Naples Federico II Naples, Italy.
4
Department of Biology and Biotechnology "Charles Darwin", Istituto Pasteur Fondazione Cenci Bolognetti, University of Rome La Sapienza Rome, Italy.
5
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples Naples, Italy ; IRCCS, Multimedica Milano, Italy.
6
Department of Pharmacy - Pharmaceutical Sciences, University of Bari Bari, Italy.
7
Department of Biology, University of Naples Federico II Naples, Italy.

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.

KEYWORDS:

5-HT7 receptor; Cdc42; actin dynamics; axonal elongation; mTOR; neurite outgrowth

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