Serotonin 2A receptor regulates microtubule assembly and induces dynamics of dendritic growth cones in rat cortical neurons in vitro.
Serotonin (5-HT) regulates the development of cerebral cortex, but 5-HT receptors mediating the effects are poorly understood. We investigated roles of 5-HT2A receptor in dendritic growth cones using dissociation culture of rat cerebral cortex. Neurons at embryonic day 16 were cultured for 4 days and treated with 5-HT2A/2C receptor agonist (DOI) for 4h. DOI increased the size of growth cone periphery which was actin-rich and microtubule-associated protein 2-negative at the dendritic tip. The length increase of the growth cone periphery may be mediated by 5-HT2A receptor, because the 5-HT2A receptor antagonist reversed the effects of DOI. Moreover, the time-lapse analysis demonstrated the increase of morphological dynamics in dendritic growth cones by DOI. Next, to elucidate the mechanisms underlying the actions of 5-HT2A receptor in dendritic growth cones, we examined the cytoskeletal proteins, tyrosinated α-tubulin (Tyr-T; dynamic tubulin) and acetylated α-tubulin (Ace-T; stable tubulin). DOI increased the fluorescence intensity of Tyr-T, while decreased that of Ace-T in the dendritic growth cone periphery. These effects were reversed by the 5-HT2A receptor antagonist, suggesting that 5-HT2A receptor promotes microtubule dynamics. In summary, it was suggested that 5-HT2A receptor induces morphological changes and dynamics of dendritic growth cones through regulation of microtubule assembly.
University of Tsukuba, Graduate School of Comprehensive Human Sciences, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
Akiko
A
Ohtani
University of Tsukuba, Graduate School of Comprehensive Human Sciences, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
Naoki
N
Kozono
University of Tsukuba, Graduate School of Comprehensive Human Sciences, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
Kouji
K
Senzaki
University of Tsukuba, Graduate School of Comprehensive Human Sciences, 1-1-1 Tennodai, Tsukuba 305-8577, Japan. Electronic address: tshiga@md.tsukuba.ac.jp.
Takashi
T
Shiga
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology*; D003599:Cytoskeleton / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008870:Microtubules / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology
D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists
Cerebral cortex; Cytoskeleton; Dendrite; Serotonin