Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein

Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein

Summary: The absence of FMR1 protein (FMRP) causes fragile X syndrome (FXS) and disturbed FMRP function is implicated in several forms of human psychopathology. We show that intracellular calcium responses to depolarization are augmented in neural progenitors derived from human induced pluripotent s...

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Main Authors: Claudia Danesi, Venkat Swaroop Achuta, Padraic Corcoran, Ulla-Kaisa Peteri, Giorgio Turconi, Nobuaki Matsui, Ilyas Albayrak, Veronika Rezov, Anders Isaksson, Maija L. Castrén
Format: Article
Language:English
Published: Elsevier 2018-12-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671118304715
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spelling doaj-1bf7a564633444628e9cb7fd14e9d9032020-11-24T22:05:11ZengElsevierStem Cell Reports2213-67112018-12-0111614491461Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation ProteinClaudia Danesi0Venkat Swaroop Achuta1Padraic Corcoran2Ulla-Kaisa Peteri3Giorgio Turconi4Nobuaki Matsui5Ilyas Albayrak6Veronika Rezov7Anders Isaksson8Maija L. Castrén9Faculty of Medicine, Physiology, University of Helsinki, PO Box 63, FIN-00014 University of Helsinki, Helsinki, FinlandFaculty of Medicine, Physiology, University of Helsinki, PO Box 63, FIN-00014 University of Helsinki, Helsinki, FinlandArray and Analysis Facility, Department of Medical Sciences, Uppsala University, PO Box 3056, 75003 Uppsala, SwedenFaculty of Medicine, Physiology, University of Helsinki, PO Box 63, FIN-00014 University of Helsinki, Helsinki, FinlandFaculty of Medicine, Physiology, University of Helsinki, PO Box 63, FIN-00014 University of Helsinki, Helsinki, FinlandDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, 770-8514, JapanFaculty of Medicine, Physiology, University of Helsinki, PO Box 63, FIN-00014 University of Helsinki, Helsinki, FinlandFaculty of Medicine, Physiology, University of Helsinki, PO Box 63, FIN-00014 University of Helsinki, Helsinki, FinlandArray and Analysis Facility, Department of Medical Sciences, Uppsala University, PO Box 3056, 75003 Uppsala, SwedenFaculty of Medicine, Physiology, University of Helsinki, PO Box 63, FIN-00014 University of Helsinki, Helsinki, Finland; Corresponding authorSummary: The absence of FMR1 protein (FMRP) causes fragile X syndrome (FXS) and disturbed FMRP function is implicated in several forms of human psychopathology. We show that intracellular calcium responses to depolarization are augmented in neural progenitors derived from human induced pluripotent stem cells and mouse brain with FXS. Increased calcium influx via nifedipine-sensitive voltage-gated calcium (Cav) channels contributes to the exaggerated responses to depolarization and type 1 metabotropic glutamate receptor activation. The ratio of L-type/T-type Cav channel expression is increased in FXS progenitors and correlates with enhanced progenitor differentiation to glutamate-responsive cells. Genetic reduction of brain-derived neurotrophic factor in FXS mouse progenitors diminishes the expression of Cav channels and activity-dependent responses, which are associated with increased phosphorylation of the phospholipase C-γ1 site within TrkB receptors and changes of differentiating progenitor subpopulations. Our results show developmental effects of increased calcium influx via L-type Cav channels in FXS neural progenitors. : In this article, Maija Castrén and colleagues show contribution of increased Ca2+ influx through L-type voltage-gated calcium channels to augmented responses to depolarization and glutamate receptor activation in neural progenitors derived from human induced pluripotent stem cells (iPSCs) and mouse brain modeling fragile X syndrome. Keywords: voltage-gated calcium channels, BDNF, fragile X syndrome, glutamate receptors, intracellular calcium, neural progenitorshttp://www.sciencedirect.com/science/article/pii/S2213671118304715
collection DOAJ
language English
format Article
sources DOAJ
author Claudia Danesi
Venkat Swaroop Achuta
Padraic Corcoran
Ulla-Kaisa Peteri
Giorgio Turconi
Nobuaki Matsui
Ilyas Albayrak
Veronika Rezov
Anders Isaksson
Maija L. Castrén
spellingShingle Claudia Danesi
Venkat Swaroop Achuta
Padraic Corcoran
Ulla-Kaisa Peteri
Giorgio Turconi
Nobuaki Matsui
Ilyas Albayrak
Veronika Rezov
Anders Isaksson
Maija L. Castrén
Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein
Stem Cell Reports
author_facet Claudia Danesi
Venkat Swaroop Achuta
Padraic Corcoran
Ulla-Kaisa Peteri
Giorgio Turconi
Nobuaki Matsui
Ilyas Albayrak
Veronika Rezov
Anders Isaksson
Maija L. Castrén
author_sort Claudia Danesi
title Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein
title_short Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein
title_full Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein
title_fullStr Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein
title_full_unstemmed Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein
title_sort increased calcium influx through l-type calcium channels in human and mouse neural progenitors lacking fragile x mental retardation protein
publisher Elsevier
series Stem Cell Reports
issn 2213-6711
publishDate 2018-12-01
description Summary: The absence of FMR1 protein (FMRP) causes fragile X syndrome (FXS) and disturbed FMRP function is implicated in several forms of human psychopathology. We show that intracellular calcium responses to depolarization are augmented in neural progenitors derived from human induced pluripotent stem cells and mouse brain with FXS. Increased calcium influx via nifedipine-sensitive voltage-gated calcium (Cav) channels contributes to the exaggerated responses to depolarization and type 1 metabotropic glutamate receptor activation. The ratio of L-type/T-type Cav channel expression is increased in FXS progenitors and correlates with enhanced progenitor differentiation to glutamate-responsive cells. Genetic reduction of brain-derived neurotrophic factor in FXS mouse progenitors diminishes the expression of Cav channels and activity-dependent responses, which are associated with increased phosphorylation of the phospholipase C-γ1 site within TrkB receptors and changes of differentiating progenitor subpopulations. Our results show developmental effects of increased calcium influx via L-type Cav channels in FXS neural progenitors. : In this article, Maija Castrén and colleagues show contribution of increased Ca2+ influx through L-type voltage-gated calcium channels to augmented responses to depolarization and glutamate receptor activation in neural progenitors derived from human induced pluripotent stem cells (iPSCs) and mouse brain modeling fragile X syndrome. Keywords: voltage-gated calcium channels, BDNF, fragile X syndrome, glutamate receptors, intracellular calcium, neural progenitors
url http://www.sciencedirect.com/science/article/pii/S2213671118304715
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