Store-operated calcium entry in disease: Beyond STIM/Orai expression levels

Kappel, Sven; Borgström, Anna; Stokłosa, Paulina; Dörr, Kathrin; Peinelt, Christine

doi:10.1016/j.semcdb.2019.01.003

Cited by 27 publications

(38 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 101 , 102 The function of these SOCCs is dependent on the intraluminal ER Ca 2+ concentration. 103 Stromal interaction molecule (STIM) proteins were identified as Ca 2+ sensors in the ER. 104 There are two homologs of STIM proteins, STIM1 and STIM2 in vertebrates that are expressed in a variety of tissues and organs including nervous tissue.…”

Section: Er Ca 2+ Regulation and The Impact On Paimentioning

confidence: 99%

“… 112 Various mechanisms, such as glycosylation and pH sensing, and proteins, including golli proteins and septins, can further regulate SOCE. 103 Through the formation of ER:plasma membrane microdomains, the ER—an intracellular Ca 2+ store—becomes functionally linked to the extracellular supply of Ca 2+ . An extensive review of SOCE and its regulatory mechanisms can be found elsewhere.…”

Section: Er Ca 2+ Regulation and The Impact On Paimentioning

confidence: 99%

See 1 more Smart Citation

Endoplasmic reticulum–mitochondria interplay in chronic pain: The calcium connection

et al. 2020

View full text Add to dashboard Cite

Chronic pain is a debilitating condition that affects roughly a third to a half of the world’s population. Despite its substantial effect on society, treatment for chronic pain is modest, at best, notwithstanding its side effects. Hence, novel therapeutics are direly needed. Emerging evidence suggests that calcium plays an integral role in mediating neuronal plasticity that underlies sensitization observed in chronic pain states. The endoplasmic reticulum and the mitochondria are the largest calcium repositories in a cell. Here, we review how stressors, like accumulation of misfolded proteins and oxidative stress, influence endoplasmic reticulum and mitochondria function and contribute to chronic pain. We further examine the shuttling of calcium across the mitochondrial-associated membrane as a mechanism of cross-talk between the endoplasmic reticulum and the mitochondria. In addition, we discuss how endoplasmic reticulum stress, mitochondrial impairment, and calcium dyshomeostasis are implicated in various models of neuropathic pain. We propose a novel framework of endoplasmic reticulum–mitochondria signaling in mediating pain hypersensitivity. These observations require further investigation in order to develop novel therapies for chronic pain.

show abstract

Section: Er Ca 2+ Regulation and The Impact On Paimentioning

confidence: 99%

Section: Er Ca 2+ Regulation and The Impact On Paimentioning

confidence: 99%

Endoplasmic reticulum–mitochondria interplay in chronic pain: The calcium connection

et al. 2020

View full text Add to dashboard Cite

show abstract

“…According to this work, targeting of SOCE partner protein POST with miR-150 could therefore represent a new treatment against auto-immune diseases. Since SOCE has been proposed to play a critical role in many human diseases, including cancer, its targeting is of the utmost importance [97,98]. However, due to the fact that SOCE is found in almost all cell types and organs, specific targeting of a given cell subtype presents a real challenge for any new potential treatment.…”

Section: Capacitative Calcium Entry (Cce) and Associated Proteinsmentioning

confidence: 99%

Partners in Crime: Towards New Ways of Targeting Calcium Channels

Noyer

Lemonnier

Mariot

et al. 2019

IJMS

View full text Add to dashboard Cite

The characterization of calcium channel interactome in the last decades opened a new way of perceiving ion channel function and regulation. Partner proteins of ion channels can now be considered as major components of the calcium homeostatic mechanisms, while the reinforcement or disruption of their interaction with the channel units now represents an attractive target in research and therapeutics. In this review we will focus on the targeting of calcium channel partner proteins in order to act on the channel activity, and on its consequences for cell and organism physiology. Given the recent advances in the partner proteins’ identification, characterization, as well as in the resolution of their interaction domain structures, we will develop the latest findings on the interacting proteins of the following channels: voltage-dependent calcium channels, transient receptor potential and ORAI channels, and inositol 1,4,5-trisphosphate receptor.

show abstract

“…Gain-of-function or loss-of-function mutations in STIM1 or Orai1, or alterations in expression ratios of STIM and Orai isoforms as well as aberrations in other regulatory mechanisms of SOCE pathway lead to its dysfunction [ 9 , 10 , 11 ]. The disruption of SOCE has various pathophysiological implications such as muscle, immune, and neurodegenerative disorders as well as cancer [ 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Pharmacological Characterization of 2-Aminoethyl Diphenylborinate (2-APB) Derivatives for Inhibition of Store-Operated Calcium Entry (SOCE) in MDA-MB-231 Breast Cancer Cells

Schild

Bhardwaj

Wenger

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Calcium ions regulate a wide array of physiological functions including cell differentiation, proliferation, muscle contraction, neurotransmission, and fertilization. The endoplasmic reticulum (ER) is the major intracellular Ca2+ store and cellular events that induce ER store depletion (e.g., activation of inositol 1,4,5-triphosphate (IP3) receptors) trigger a refilling process known as store-operated calcium entry (SOCE). It requires the intricate interaction between the Ca2+ sensing stromal interaction molecules (STIM) located in the ER membrane and the channel forming Orai proteins in the plasma membrane (PM). The resulting active STIM/Orai complexes form highly selective Ca2+ channels that facilitate a measurable Ca2+ influx into the cytosol followed by successive refilling of the ER by the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). STIM and Orai have attracted significant therapeutic interest, as enhanced SOCE has been associated with several cancers, and mutations in STIM and Orai have been linked to immunodeficiency, autoimmune, and muscular diseases. 2-Aminoethyl diphenylborinate (2-APB) is a known modulator and depending on its concentration can inhibit or enhance SOCE. We have synthesized several novel derivatives of 2-APB, introducing halogen and other small substituents systematically on each position of one of the phenyl rings. Using a fluorometric imaging plate reader (FLIPR) Tetra-based calcium imaging assay we have studied how these structural changes of 2-APB affect the SOCE modulation activity at different compound concentrations in MDA-MB-231 breast cancer cells. We have discovered 2-APB derivatives that block SOCE at low concentrations, at which 2-APB usually enhances SOCE.

show abstract

Store-operated calcium entry in disease: Beyond STIM/Orai expression levels

Cited by 27 publications

References 151 publications

Endoplasmic reticulum–mitochondria interplay in chronic pain: The calcium connection

Endoplasmic reticulum–mitochondria interplay in chronic pain: The calcium connection

Partners in Crime: Towards New Ways of Targeting Calcium Channels

Synthesis and Pharmacological Characterization of 2-Aminoethyl Diphenylborinate (2-APB) Derivatives for Inhibition of Store-Operated Calcium Entry (SOCE) in MDA-MB-231 Breast Cancer Cells

Contact Info

Product

Resources

About