Regulation of Calcium Signaling by STIM1 and ORAI1

Martı́n-Romero, Francisco Javier; Pascual-Caro, Carlos; Guerrero, Aida Lopez; Espinosa-Bermejo, Noelia; Pozo‐Guisado, Eulalia

doi:10.5772/intechopen.78587

Cited by 5 publications

(4 citation statements)

References 96 publications

(114 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, Mapk14 expression was significantly upregulated in Stim1 deficient ameloblasts. MAPK14 has been shown to regulate SOCE both indirectly (through TGF-β1 and NF-kappa) or directly by phosphorylating Stim1 (Martin-Romero et al, 2018). In ameloblasts, MAPK14 has been shown to play a role in regulating early tooth morphogenesis and its ectodermal tissue deletion results in abnormally shaped dental cusps and a profoundly hypoplastic enamel layer (Greenblatt et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The phosphorylated CREB translocates into the nucleus where it recognizes the CRE of the Per genes promoters and induces their expression ( Lee et al, 2010 ). Furthermore, it has been shown that SOCE is essential for activating CREB in multiple tissues including smooth muscles and immune cells ( Avila-Medina et al, 2018 ; Martin-Romero et al, 2018 ). The fact that SOCE-deficient ameloblast showed significantly lowered levels of the Per 2 genes suggests that control of CREB activity may represent one of the main mechanisms by which SOCE can directly affect the circadian TTFLs in ameloblasts, similar to the SCN and other cells ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Calcium Sets the Clock in Ameloblasts

et al. 2020

View full text Add to dashboard Cite

Background: Stromal interaction molecule 1 (STIM1) is one of the main components of the store operated Ca 2+ entry (SOCE) signaling pathway. Individuals with mutated STIM1 present severely hypomineralized enamel characterized as amelogenesis imperfecta (AI) but the downstream molecular mechanisms involved remain unclear. Circadian clock signaling plays a key role in regulating the enamel thickness and mineralization, but the effects of STIM1-mediated AI on circadian clock are unknown. Objectives: The aim of this study is to examine the potential links between SOCE and the circadian clock during amelogenesis. Methods: We have generated mice with ameloblast-specific deletion of Stim1 (Stim1 fl/fl /Amelx-iCre +/+ , Stim1 cKO) and analyzed circadian gene expression profile in Stim1 cKO compared to control (Stim1 fl/fl /Amelx-iCre −/−) using ameloblast microdissection and RNA micro-array of 84 circadian genes. Expression level changes were validated by qRT-PCR and immunohistochemistry. Results: Stim1 deletion has resulted in significant upregulation of the core circadian activator gene Brain and Muscle Aryl Hydrocarbon Receptor Nuclear Translocation 1 (Bmal1) and downregulation of the circadian inhibitor Period 2 (Per2). Our analyses also revealed that SOCE disruption results in dysregulation of two additional circadian regulators; p38α mitogen-activated protein kinase (MAPK14) and transforming growth factor-beta1 (TGF-β1). Both MAPK14 and TGF-β1 pathways are known to play major roles in enamel secretion and their dysregulation has been previously implicated in the development of AI phenotype. Conclusion: These data indicate that disruption of SOCE significantly affects the ameloblasts molecular circadian clock, suggesting that alteration of the circadian clock may be partly involved in the development of STIM1-mediated AI.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Calcium Sets the Clock in Ameloblasts

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Oligomers of active STIM1 are less mobile and phospho-STIM1 is found at the cell periphery[10], close to the plasma membrane, where it binds ORAI1. Because STIM1 and ORAI1 are ubiquitous, they are involved in a wide range of signaling pathways that regulate many cellular functions[11]. However, the number of studies about the role of STIM1 in neuronal tissue is much more limited.…”

Section: Stim1 and Calcium Mobilizationmentioning

confidence: 99%

Role of STIM1 in neurodegeneration

Pascual-Caro¹,

Espinosa-Bermejo²,

Pozo‐Guisado³

et al. 2018

WJBC

Self Cite

View full text Add to dashboard Cite

STIM1 is an endoplasmic reticulum (ER) protein with a key role in Ca2+ mobilization. Due to its ability to act as an ER-intraluminal Ca2+ sensor, it regulates store-operated Ca2+ entry (SOCE), which is a Ca2+ influx pathway involved in a wide variety of signalling pathways in eukaryotic cells. Despite its important role in Ca2+ transport, current knowledge about the role of STIM1 in neurons is much more limited. Growing evidence supports a role for STIM1 and SOCE in the preservation of dendritic spines required for long-term potentiation and the formation of memory. In this regard, recent studies have demonstrated that the loss of STIM1, which impairs Ca2+ mobilization in neurons, risks cell viability and could be the cause of neurodegenerative diseases. The role of STIM1 in neurodegeneration and the molecular basis of cell death triggered by low levels of STIM1 are discussed in this review.

show abstract

“…Consequently, Ca 2+ influx through STIM1-regulated channels is referred to as store-operated Ca 2+ entry (SOCE). This influx of extracellular Ca 2+ modulates numerous cellular events, such as cortical cytoskeleton reorganization, cell migration, the cell cycle, and the regulation of gene expression [reviewed in ( 9 )]. This extensive regulation is attributed to the numerous Ca 2+ -dependent signaling pathways that rely on STIM1/ORAI1.…”

Section: Introductionmentioning

confidence: 99%

STIM1 translocation to the nucleus protects cells from DNA damage

Sanchez-Lopez,

Orantos-Aguilera,

Pozo-Guisado

et al. 2024

Nucleic Acids Research

Self Cite

View full text Add to dashboard Cite

DNA damage represents a challenge for cells, as this damage must be eliminated to preserve cell viability and the transmission of genetic information. To reduce or eliminate unscheduled chemical modifications in genomic DNA, an extensive signaling network, known as the DNA damage response (DDR) pathway, ensures this repair. In this work, and by means of a proteomic analysis aimed at studying the STIM1 protein interactome, we have found that STIM1 is closely related to the protection from endogenous DNA damage, replicative stress, as well as to the response to interstrand crosslinks (ICLs). Here we show that STIM1 has a nuclear localization signal that mediates its translocation to the nucleus, and that this translocation and the association of STIM1 to chromatin increases in response to mitomycin-C (MMC), an ICL-inducing agent. Consequently, STIM1-deficient cell lines show higher levels of basal DNA damage, replicative stress, and increased sensitivity to MMC. We show that STIM1 normalizes FANCD2 protein levels in the nucleus, which explains the increased sensitivity of STIM1-KO cells to MMC. This study not only unveils a previously unknown nuclear function for the endoplasmic reticulum protein STIM1 but also expands our understanding of the genes involved in DNA repair.

show abstract

Regulation of Calcium Signaling by STIM1 and ORAI1

Cited by 5 publications

References 96 publications

Calcium Sets the Clock in Ameloblasts

Calcium Sets the Clock in Ameloblasts

Role of STIM1 in neurodegeneration

STIM1 translocation to the nucleus protects cells from DNA damage

Contact Info

Product

Resources

About