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How CD40L reverse signaling regulates axon and dendrite growth

Carriba, Paulina and Davies, Alun M. ORCID: 2021. How CD40L reverse signaling regulates axon and dendrite growth. Cellular and Molecular Life Sciences 78 , pp. 1065-1083. 10.1007/s00018-020-03563-2

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CD40-activated CD40L reverse signaling is a major physiological regulator of axon and dendrite growth from developing hippocampal pyramidal neurons. Here we have studied how CD40L-mediated reverse signaling promotes the growth of these processes. Cultures of hippocampal pyramidal neurons were established from Cd40−/− mouse embryos to eliminate endogenous CD40/CD40L signaling, and CD40L reverse signaling was stimulated by a CD40-Fc chimera. CD40L reverse signaling increased phosphorylation and hence activation of proteins in the PKC, ERK, and JNK signaling pathways. Pharmacological activators and inhibitors of these pathways revealed that whereas activation of JNK inhibited growth, activation of PKC and ERK1/ERK2 enhanced growth. Experiments using combinations of pharmacological reagents revealed that these signaling pathways regulate growth by functioning as an interconnected and interdependent network rather than acting in a simple linear sequence. Immunoprecipitation studies suggested that stimulation of CD40L reverse signaling generated a receptor complex comprising CD40L, PKCβ, and the Syk tyrosine kinase. Our studies have begun to elucidate the molecular network and interactions that promote axon and dendrite growth from developing hippocampal neurons following activation of CD40L reverse signaling.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Springer Verlag (Germany)
ISSN: 1420-682X
Funders: Wellcome Trust
Date of First Compliant Deposit: 9 June 2020
Date of Acceptance: 25 May 2020
Last Modified: 06 May 2023 00:45

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