The T-type Ca 2+ Channel Ca v 3.2 Regulates Differentiation of Neural Progenitor Cells during Cortical Development via Caspase-3.

Autor: Rebellato P; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden., Kaczynska D; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden., Kanatani S; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden., Rayyes IA; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden., Zhang S; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden., Villaescusa C; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden., Falk A; Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden., Arenas E; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden., Hermanson O; Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden., Louhivuori L; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: lauri.louhivuori@ki.se., Uhlén P; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: per.uhlen@ki.se.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2019 Mar 15; Vol. 402, pp. 78-89. Date of Electronic Publication: 2019 Jan 21.
DOI: 10.1016/j.neuroscience.2019.01.015
Abstrakt: Here we report that the low-voltage-dependent T-type calcium (Ca 2+ ) channel Ca v 3.2, encoded by the CACNA1H gene, regulates neuronal differentiation during early embryonic brain development through activating caspase-3. At the onset of neuronal differentiation, neural progenitor cells exhibited spontaneous Ca 2+ activity. This activity strongly correlated with the upregulation of CACNA1H mRNA. Cells exhibiting robust spontaneous Ca 2+ signaling had increased caspase-3 activity unrelated to apoptosis. Inhibition of Ca v 3.2 by drugs or viral CACNA1H knock down resulted in decreased caspase-3 activity followed by suppressed neurogenesis. In contrast, when CACNA1H was overexpressed, increased neurogenesis was detected. Cortical slices from Cacna1h knockout mice showed decreased spontaneous Ca 2+ activity, a significantly lower protein level of cleaved caspase-3, and microanatomical abnormalities in the subventricular/ventricular and cortical plate zones when compared to their respective embryonic controls. In summary, we demonstrate a novel relationship between Ca v 3.2 and caspase-3 signaling that affects neurogenesis in the developing brain.
(Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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