Ca2+ Signaling and Calcium-Binding Proteins in Human Disease

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 31 March 2025 | Viewed by 880

Special Issue Editor


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Guest Editor
Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
Interests: calcium signalling; cardiac arrhtymia; structural biology; physiology; ion channels

Special Issue Information

Dear Colleagues,

Calcium signaling plays a crucial role in various physiological processes, and disruptions in this pathway have been implicated in several human diseases. Calcium signaling often involves the interaction of calcium ions with calcium-binding proteins (e.g., calmodulin) to transduce calcium signals into cellular responses. Aberrations in these signaling pathways have been associated with a spectrum of human diseases, including cardiac disorders, neurodegenerative conditions and immune system dysfunction. However, the precise molecular mechanisms of these diseases remain poorly understood, limiting the development of novel, efficient and targeted therapies.

For this Special Issue, we welcome all original research and review articles focusing on calcium signaling and calcium-binding proteins in the context of human disease.

Dr. Nordine Helassa
Guest Editor

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Keywords

  • calcium signaling
  • calcium-binding protein
  • calmodulin
  • ion channels
  • cardiac arrhythmia
  • neurodegenerative disease

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Published Papers (1 paper)

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Research

11 pages, 6658 KiB  
Article
Attempts to Create Transgenic Mice Carrying the Q3924E Mutation in RyR2 Ca2+ Binding Site
by Xiao-hua Zhang, Fu-lei Tang, Allison M. Trouten and Martin Morad
Cells 2024, 13(24), 2051; https://doi.org/10.3390/cells13242051 - 12 Dec 2024
Viewed by 447
Abstract
Over 200 point mutations in the ryanodine receptor (RyR2) of the cardiac sarcoplasmic reticulum (SR) are known to be associated with cardiac arrhythmia. We have already reported on the calcium signaling phenotype of a point mutation in RyR2 Ca2+ binding site Q3925E [...] Read more.
Over 200 point mutations in the ryanodine receptor (RyR2) of the cardiac sarcoplasmic reticulum (SR) are known to be associated with cardiac arrhythmia. We have already reported on the calcium signaling phenotype of a point mutation in RyR2 Ca2+ binding site Q3925E expressed in human stem-cell-derived cardiomyocytes (hiPSC-CMs) that was found to be lethal in a 9-year-old girl. CRISPR/Cas9-gene-edited mutant cardiomyocytes carrying the RyR2-Q3925E mutation exhibited a loss of calcium-induced calcium release (CICR) and caffeine-triggered calcium release but continued to beat arrhythmically without generating significant SR Ca2+ release, consistent with a remodeling of the calcium signaling pathway. An RNAseq heat map confirmed significant changes in calcium-associated genes, supporting the possibility of remodeling. To determine the in situ cardiac phenotype in an animal model of this mutation, we generated a knock-in mouse model of RyR2-Q3924E+/− using the CRISPR/Cas9 technique. We obtained three homozygous and one chimera mice, but they all died before reaching 3 weeks of age, preventing the establishment of germline mutation transmission in their offspring. A histo-pathological analysis of the heart showed significant cardiac hypertrophy, suggesting the Q3924E-RyR2 mutation was lethal to the mice. Full article
(This article belongs to the Special Issue Ca2+ Signaling and Calcium-Binding Proteins in Human Disease)
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