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

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Danesi , C , Achuta , V S , Corcoran , P , Peteri , U-K , Turconi , G , Matsui , N , Albayrak , I , Rezov , V , Isaksson , A & Castren , M L 2018 , ' Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein ' , Stem cell reports , vol. 11 , no. 6 , pp. 1449-1461 . https://doi.org/10.1016/j.stemcr.2018.11.003

Title: Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein
Author: Danesi, Claudia; Achuta, Venkat Swaroop; Corcoran, Padraic; Peteri, Ulla-Kaisa; Turconi, Giorgio; Matsui, Nobuaki; Albayrak, Ilyas; Rezov, Veronika; Isaksson, Anders; Castren, Maija L.
Contributor: University of Helsinki, Department of Physiology
University of Helsinki, Medicum
University of Helsinki, Department of Physiology
University of Helsinki, Department of Physiology
University of Helsinki, Department of Physiology
University of Helsinki, Medicum
Date: 2018-12-11
Language: eng
Number of pages: 13
Belongs to series: Stem cell reports
ISSN: 2213-6711
URI: http://hdl.handle.net/10138/287691
Abstract: 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 (Ca-v) channels contributes to the exaggerated responses to depolarization and type 1 metabotropic glutamate receptor activation. The ratio of L-type/T-type Ca-v 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 Ca-v channels and activity-dependent responses, which are associated with increased phosphorylation of the phospholipase C-gamma 1 site within TrkB receptors and changes of differentiating progenitor subpopulations. Our results show developmental effects of increased calcium influx via L-type Ca-v channels in FXS neural progenitors.
Subject: METABOTROPIC GLUTAMATE-RECEPTOR
CALPASTATIN DOMAIN-L
NEURONAL MIGRATION
MODEL
DIFFERENTIATION
EXPRESSION
RESPONSES
CELLS
NEOCORTEX
CA(V)1.2
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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