Next Article in Journal
Tissues and Tumor Microenvironment (TME) in 3D: Models to Shed Light on Immunosuppression in Cancer
Previous Article in Journal
Allotetraploidization in Brachypodium May Have Led to the Dominance of One Parent’s Metabolome in Germinating Seeds
 
 
Article

Signalling Pathways Mediating the Effects of CD40-Activated CD40L Reverse Signalling on Inhibitory Medium Spiny Neuron Neurite Growth

School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK
*
Author to whom correspondence should be addressed.
Academic Editors: Lin-Hua Jiang and Kai Kaila
Cells 2021, 10(4), 829; https://doi.org/10.3390/cells10040829
Received: 11 February 2021 / Revised: 15 March 2021 / Accepted: 2 April 2021 / Published: 7 April 2021
(This article belongs to the Section Cells of the Nervous System)
CD40-activated CD40L-mediated reverse signalling is a major physiological regulator of neurite growth from excitatory and inhibitory neurons in the developing central nervous system (CNS). Whereas in excitatory pyramidal neurons, CD40L reverse signalling promotes the growth and elaboration of dendrites and axons, in inhibitory GABAergic striatal medium spiny neurons (MSNs), it restricts neurite growth and branching. In pyramidal neurons, we previously reported that CD40L reverse signalling activates an interconnected and interdependent signalling network involving protein kinase C (PKC), extracellular regulated kinases 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK) signalling pathways that regulates dendrite and axon growth. Here, we have studied whether these signalling pathways also influence neurite growth from striatal inhibitory MSNs. To unequivocally activate CD40L reverse signalling, we treated MSN cultures from CD40-deficient mice with CD40-Fc. Here, we report that activation of CD40L reverse signalling in these cultures also increased the phosphorylation of PKC, ERK1/2, and JNK. Using pharmacological activators and inhibitors of these signalling pathways singularly and in combination, we have shown that, as in pyramidal neurons, these signalling pathways work in an interconnected and interdependent network to regulate the neurite growth, but their functions, relationships, and interdependencies are different from those observed in pyramidal neurons. Furthermore, immunoprecipitation studies showed that stimulation of CD40L reverse signalling recruits the catalytic fragment of Syk tyrosine kinase, but in contrast to pyramidal neurons, PKC does not participate in this recruitment. Our findings show that distinctive networks of three signalling pathways mediate the opposite effects of CD40L reverse signalling on neurite growth in excitatory and inhibitory neurons. View Full-Text
Keywords: CD40L-reverse signalling; neurite growth; inhibitory neuron; PKC; JNK; ERK1/2; Syk CD40L-reverse signalling; neurite growth; inhibitory neuron; PKC; JNK; ERK1/2; Syk
Show Figures

Figure 1

MDPI and ACS Style

Carriba, P.; Davies, A.M. Signalling Pathways Mediating the Effects of CD40-Activated CD40L Reverse Signalling on Inhibitory Medium Spiny Neuron Neurite Growth. Cells 2021, 10, 829. https://doi.org/10.3390/cells10040829

AMA Style

Carriba P, Davies AM. Signalling Pathways Mediating the Effects of CD40-Activated CD40L Reverse Signalling on Inhibitory Medium Spiny Neuron Neurite Growth. Cells. 2021; 10(4):829. https://doi.org/10.3390/cells10040829

Chicago/Turabian Style

Carriba, Paulina, and Alun M. Davies. 2021. "Signalling Pathways Mediating the Effects of CD40-Activated CD40L Reverse Signalling on Inhibitory Medium Spiny Neuron Neurite Growth" Cells 10, no. 4: 829. https://doi.org/10.3390/cells10040829

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop