Coronin-1 and calcium signaling governs sympathetic final target innervation

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Dong SuoChristopher D Deppmann

Abstract

Development of a functional peripheral nervous system requires axons to rapidly innervate and arborize into final target organs and then slow but not halt their growth to establish stable connections while keeping pace with organ growth. Here we examine the role of the NGF-TrkA effector protein, Coronin-1, on postganglionic sympathetic neuron final target innervation. In the absence of Coronin-1 we find that NGF-TrkA-PI3K signaling drives robust axon growth and branching in part by suppressing GSK3β. In contrast, the presence of Coronin-1 (wild-type neurons) suppresses but does not halt NGF-TrkA-dependent growth and branching. This relative suppression in axon growth behaviors is due to Coronin-1-dependent calcium release via PLC-γ1 signaling, which releases PI3K-dependent suppression of GSK3β. Finally, we demonstrate that Coro1a(-/-) mice display sympathetic axon overgrowth and overbranching phenotypes in the developing heart. Together with previous work demonstrating the Coronin-1 expression is NGF dependent, this work suggests that periods before and after NGF-TrkA-induced Coronin-1 expression (and likely other factors) defines two distinct axon growth states, which are critical for proper circuit formation in the sympatheti...Continue Reading

Citations

Jul 15, 2015·PloS One·Kimberly R HagelCharles R Tessier
Aug 10, 2016·Developmental Neurobiology·Kelly BarfordBettina Winckler
Dec 14, 2018·The Journal of Cell Biology·Maria M BagonisGaudenz Danuser
Apr 21, 2020·Drug Design, Development and Therapy·Ting WangPeng Xie
Mar 20, 2018·Scientific Reports·Kelly BarfordBettina Winckler
Dec 31, 2020·Molecular Biology of the Cell·Shalini MenonStephanie L Gupton

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