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Article

Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation

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Instituto de Neurociencias de Castilla y León (INCYL), Universidad de Salamanca, 37007 Salamanca, Spain
2
Departamento de Fisiología, Universidad de Sevilla, 41012 Sevilla, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8852; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228852
Received: 4 November 2020 / Revised: 20 November 2020 / Accepted: 20 November 2020 / Published: 23 November 2020
Neural progenitor cells (NPCs) are self-renewing cells that give rise to the major cells in the nervous system and are considered to be the possible cell of origin of glioblastoma. The gap junction protein connexin43 (Cx43) is expressed by NPCs, exerting channel-dependent and -independent roles. We focused on one property of Cx43—its ability to inhibit Src, a key protein in brain development and oncogenesis. Because Src inhibition is carried out by the sequence 266–283 of the intracellular C terminus in Cx43, we used a cell-penetrating peptide containing this sequence, TAT-Cx43266–283, to explore its effects on postnatal subventricular zone NPCs. Our results show that TAT-Cx43266–283 inhibited Src activity and reduced NPC proliferation and survival promoted by epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). In differentiation conditions, TAT-Cx43266–283 increased astrocyte differentiation at the expense of neuronal differentiation, which coincided with a reduction in Src activity and β-catenin expression. We propose that Cx43, through the region 266–283, reduces Src activity, leading to disruption of EGF and FGF-2 signaling and to down-regulation of β-catenin with effects on proliferation and differentiation. Our data indicate that the inhibition of Src might contribute to the complex role of Cx43 in NPCs and open new opportunities for further research in gliomagenesis. View Full-Text
Keywords: neural progenitor cells; neurons; astrocytes; ß-catenin; glioma stem cells; connexin; neural precursors; Cx43 neural progenitor cells; neurons; astrocytes; ß-catenin; glioma stem cells; connexin; neural precursors; Cx43
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MDPI and ACS Style

Talaverón, R.; Matarredona, E.R.; Herrera, A.; Medina, J.M.; Tabernero, A. Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation. Int. J. Mol. Sci. 2020, 21, 8852. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228852

AMA Style

Talaverón R, Matarredona ER, Herrera A, Medina JM, Tabernero A. Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation. International Journal of Molecular Sciences. 2020; 21(22):8852. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228852

Chicago/Turabian Style

Talaverón, Rocío, Esperanza R. Matarredona, Alejandro Herrera, José M. Medina, and Arantxa Tabernero. 2020. "Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation" International Journal of Molecular Sciences 21, no. 22: 8852. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228852

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