English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Fragile X syndrome (FXS), the most common form of inherited intellectual disability (ID) and a leading cause of autism, results from the loss of expression of the  Fmr1  gene which encodes the RNA-binding protein Fragile X Mental Retardation Protein (FMRP). Among the thousands mRNA targets of FMRP, numerous encode regulators of ion homeostasis. It has also been described that FMRP directly interacts with Ca 2+  channels modulating their activity. Collectively these findings suggest that FMRP plays critical roles in Ca 2+  homeostasis during nervous system development. We carried out a functional analysis of Ca 2+  regulation using a calcium imaging approach in  Fmr1 -KO cultured neurons and we show that these cells display impaired steady state Ca 2+  concentration and an altered entry of Ca 2+  after KCl-triggered depolarization. Consistent with these data, we show that the protein product of the  Cacna1a  gene, the pore-forming subunit of the Ca v 2.1 channel, is less expressed at the plasma membrane of  Fmr1 -KO neurons compared to wild-type (WT). Thus, our findings point out the critical role that Ca v 2.1 plays in the altered Ca 2+  flux in  Fmr1 -KO neurons, impacting Ca 2+  homeostasis of these cells. Remarkably, we highlight a new phenotype of cultured  Fmr1 -KO neurons that can be considered a novel cellular biomarker and is amenable to small molecule screening and identification of new drugs to treat FXS.

New Insights Into the Role of Cav2 Protein Family in Calcium Flux Deregulation in Fmr1-KO Neurons