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T-type Ca 2+ channels are required for enhanced sympathetic axon growth by TNFα reverse signalling

Kisiswa, Lilian, Erice Jurecky, Clara, Ferron, Laurent, Wyatt, Sean ORCID:, Osório, Catarina, Dolphin, Annette C. and Davies, Alun M. ORCID: 2017. T-type Ca 2+ channels are required for enhanced sympathetic axon growth by TNFα reverse signalling. Open Biology 7 (1) , 160288. 10.1098/rsob.160288

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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 Ca2+ influx, and highly selective T-type Ca2+ channel inhibitors, but not pharmacological inhibitors of L-type, N-type and P/Q-type Ca2+ channels, prevented enhanced axon growth. T-type Ca2+ channel-specific inhibitors eliminated Ca2+ 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 Ca2+ channels along sympathetic axons, which is required for enhanced axon growth.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Uncontrolled Keywords: development; reverse signalling; sympathetic neuron; axon growth; TNFα; Ca2+ channels
Publisher: The Royal Society
ISSN: 20462441
Funders: Wellcome Trust
Date of First Compliant Deposit: 15 March 2017
Date of Acceptance: 12 December 2016
Last Modified: 04 May 2023 13:21

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