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T-type Ca2+ channels are required for enhanced sympathetic axon growth by TNFα reverse signalling

Kisiswa, L; Erice, C; Ferron, L; Wyatt, S; Osório, C; Dolphin, AC; Davies, AM; (2017) T-type Ca2+ channels are required for enhanced sympathetic axon growth by TNFα reverse signalling. Open Biology , 7 , Article 160288. 10.1098/rsob.160288. Green open access

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Abstract

Tumour necrosis factor receptor 1 (TNFR1)-activated TNFα reverse signalling, in which membrane-integrated TNFα functions as a receptor for TNFR1, enhances axon growth from developing sympathetic neurons and plays a crucial role in establishing sympathetic innervation. Here, we have investigated the link between TNFα reverse signalling and axon growth in cultured sympathetic neurons. TNFR1-activated TNFα reverse signalling promotes Ca(2+) influx, and highly selective T-type Ca(2+) channel inhibitors, but not pharmacological inhibitors of L-type, N-type and P/Q-type Ca(2+) channels, prevented enhanced axon growth. T-type Ca(2+) channel-specific inhibitors eliminated Ca(2+) spikes promoted by TNFα reverse signalling in axons and prevented enhanced axon growth when applied locally to axons, but not when applied to cell somata. Blocking action potential generation did not affect the effect of TNFα reverse signalling on axon growth, suggesting that propagated action potentials are not required for enhanced axon growth. TNFα reverse signalling enhanced protein kinase C (PKC) activation, and pharmacological inhibition of PKC prevented the axon growth response. These results suggest that TNFα reverse signalling promotes opening of T-type Ca(2+) channels along sympathetic axons, which is required for enhanced axon growth.

Type: Article
Title: T-type Ca2+ channels are required for enhanced sympathetic axon growth by TNFα reverse signalling
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1098/rsob.160288
Publisher version: https://doi.org/10.1098/rsob.160288
Language: English
Additional information: Copyright © 2017 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, provided the original author and source are credited.
Keywords: Ca2+ channels, TNFα, axon growth, development, reverse signalling, sympathetic neuron
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1538684
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