5-ht6 receptor-mediated morphological changes via rho family-dependent pathways

5-ht6 receptor-mediated morphological changes via rho family-dependent pathways
Rho GTPase; dendritic spine; synaptic plasticity
Issue Date
40th Annual Meeting Neuroscience 2010
The Rho family (RhoA, Cdc42, and Rac1) of small GTPases is one of the best-known cytoskeleton regulators and mainly affects synaptic plasticity via regulation of dendritic spines on post-synaptic sites in the brain. Synaptic plasticity is one of key phenomena showing how connections between neurons dynamically change in strength under pathological condition as well as normal physiological condition. However, regulators that couple with Rho GTPases in the central nervous system (CNS) have not yet been fully understood. Herein, we demonstrated that 5-hydroxytryptamine6 receptor (5-HT6R), a 7 helical transmembrane G protein-coupled receptor (GPCR), induced cytoskeleton rearrangement in the cloned cell lines and its effects were mediated via RhoA in an agonist-dependent manner, whereas Rac1 and Cdc42 was not involved in the 5-HT6R-mediated morphological changes. Furthermore, we found that 5-HT6R also caused an increase in RhoA activities in cultured primary neurons. To confirm the roles of 5-HT6R on dendritic spines, we examined that 5-HT6R localized on post-synaptic sites, not on pre-synaptic sites, and the modulation of dendritic spines by the stimulation of 5-HT6R in cultured hippocampal neurons. These data imply that 5-HT6R may have a pivotal role on formation of dendritic spines via RhoA-dependent pathways, leading to changes in strength between neuron and neuron.
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