Photoactivated adenylyl cyclase (PAC) reveals novel mechanisms underlying cAMP-dependent axonal morphogenesis

Scientific Reports
Zhiwen ZhouRyuta Koyama

Abstract

Spatiotemporal regulation of axonal branching and elongation is essential in the development of refined neural circuits. cAMP is a key regulator of axonal growth; however, whether and how intracellular cAMP regulates axonal branching and elongation remain unclear, mainly because tools to spatiotemporally manipulate intracellular cAMP levels have been lacking. To overcome this issue, we utilized photoactivated adenylyl cyclase (PAC), which produces cAMP in response to blue-light exposure. In primary cultures of dentate granule cells transfected with PAC, short-term elevation of intracellular cAMP levels induced axonal branching but not elongation, whereas long-term cAMP elevation induced both axonal branching and elongation. The temporal dynamics of intracellular cAMP levels regulated axonal branching and elongation through the activation of protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac), respectively. Thus, using PAC, our study for the first time reveals that temporal cAMP dynamics could regulate axonal branching and elongation via different signaling pathways.

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Citations

Jun 3, 2016·Biological & Pharmaceutical Bulletin·Ryuta Koyama
Feb 14, 2017·Nature Chemical Biology·Kirill GorshkovJin Zhang
Feb 2, 2018·The Journal of Physiology·Yasin B SevenGordon S Mitchell
Mar 15, 2018·Physiological Reviews·William G Robichaux, Xiaodong Cheng
Oct 12, 2018·Endocrinology·Su Young HanAllan E Herbison
Jun 14, 2018·Frontiers in Neurology·Ryuta Koyama, Yuji Ikegaya
Feb 15, 2019·International Journal of Molecular Sciences·Zhiwen ZhouRyuta Koyama
Jul 30, 2019·Cell Chemical Biology·Colin P O'BanionDavid S Lawrence
Jan 17, 2021·Proceedings of the National Academy of Sciences of the United States of America·Zhiwen ZhouRyuta Koyama
Jul 4, 2019·Progress in Biophysics and Molecular Biology·Francesca GrisanKonstantinos Lefkimmiatis
May 13, 2020·Oncology Reviews·Seidu A Richard
Nov 3, 2017·Neuron·Benjamin R RostPeter Hegemann

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Methods Mentioned

BETA
ELISA
GTPase
transfection

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