Short Novel STIM1B Uncovers a Mechanism of Synaptic Enhancement

Ramesh, Girish; Jarzembowksi, Lukas; Schwarz, Yvonne; Konrad, Maik; Poth, Vanessa; Schwaer, Gertrud; Lauer, Anna Andrea; Grimm, Marcus O. W.; Alansary, Dalia; Bruns, Dieter; Niemeyer, Barbara A.

doi:10.2139/ssrn.3707638

Cited by 2 publications

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“…1D, E) levels showed that both naïve and memory CD4 + cells express comparable levels of SOCE components. The specificity of the antibodies was validated by cells where ORAI1 (Alansary, Peckys et al, 2020), STIM1 or STIM2 (Ramesh, Jarzembowski et al, 2021) were deleted by CRISPR-Cas9 mediated gene targeting. Using commercially available antibodies for ORAI2 and ORAI3 proteins we were unable to reliably detect endogenous proteins.…”

Section: Resultsmentioning

confidence: 99%

Plasma Membrane Calcium ATPase (PMCA) Regulates Stoichiometry of CD4⁺T-cell Compartments

Merino-Wong

Niemeyer

Alansary

2021

Preprint

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Immune responses involve mobilization of T cells within naïve and memory compartments. Tightly regulated Ca2+ levels are essential for balanced immune outcomes. How Ca2+ contributes to regulating compartment stoichiometry is unknown. Here, we show that plasma membrane Ca2+ ATPase 4 (PMCA4) is differentially expressed in human CD4+ T compartments yielding distinct store operated Ca2+ entry (SOCE) profiles. Modulation of PMCA4 yielded a more prominent increase of SOCE in memory than in naïve CD4+ T cell. Interestingly, downregulation of PMCA4 reduced the effector compartment fraction and led to accumulation of cells in the naïve compartment. In silico analysis and chromatin immunoprecipitation unraveled Ying Yang 1 (YY1) as a transcription factor regulating PMCA4 expression. Analyses of PMCA and YY1 expression patterns following activation and of PMCA promoter activity following downregulation of YY1 highlight repressive role of YY1 on PMCA expression. Our findings show that under the transcriptional control by YY1, PMCA4 adapts Ca2+ levels to cellular requirements during effector and quiescent phases and thereby represent a potential target to intervene with the outcome of the immune response.

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Section: Resultsmentioning

confidence: 99%

Plasma Membrane Calcium ATPase (PMCA) Regulates Stoichiometry of CD4⁺T-cell Compartments

Merino-Wong

Niemeyer

Alansary

2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Plasma Membrane Calcium ATPase Regulates Stoichiometry of CD4+ T-Cell Compartments

2021

Self Cite

View full text Add to dashboard Cite

Immune responses involve mobilization of T cells within naïve and memory compartments. Tightly regulated Ca2+ levels are essential for balanced immune outcomes. How Ca2+ contributes to regulating compartment stoichiometry is unknown. Here, we show that plasma membrane Ca2+ ATPase 4 (PMCA4) is differentially expressed in human CD4+ T compartments yielding distinct store operated Ca2+ entry (SOCE) profiles. Modulation of PMCA4 yielded a more prominent increase of SOCE in memory than in naïve CD4+ T cell. Interestingly, downregulation of PMCA4 reduced the effector compartment fraction and led to accumulation of cells in the naïve compartment. In silico analysis and chromatin immunoprecipitation point towards Ying Yang 1 (YY1) as a transcription factor regulating PMCA4 expression. Analyses of PMCA and YY1 expression patterns following activation and of PMCA promoter activity following downregulation of YY1 highlight repressive role of YY1 on PMCA expression. Our findings show that PMCA4 adapts Ca2+ levels to cellular requirements during effector and quiescent phases and thereby represent a potential target to intervene with the outcome of the immune response.

show abstract

Short Novel STIM1B Uncovers a Mechanism of Synaptic Enhancement

Cited by 2 publications

References 0 publications

Plasma Membrane Calcium ATPase (PMCA) Regulates Stoichiometry of CD4⁺T-cell Compartments

Plasma Membrane Calcium ATPase (PMCA) Regulates Stoichiometry of CD4⁺T-cell Compartments

Plasma Membrane Calcium ATPase Regulates Stoichiometry of CD4+ T-Cell Compartments

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Short Novel STIM1B Uncovers a Mechanism of Synaptic Enhancement

Cited by 2 publications

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Plasma Membrane Calcium ATPase (PMCA) Regulates Stoichiometry of CD4+T-cell Compartments

Plasma Membrane Calcium ATPase (PMCA) Regulates Stoichiometry of CD4+T-cell Compartments

Plasma Membrane Calcium ATPase Regulates Stoichiometry of CD4+ T-Cell Compartments

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Plasma Membrane Calcium ATPase (PMCA) Regulates Stoichiometry of CD4⁺T-cell Compartments

Plasma Membrane Calcium ATPase (PMCA) Regulates Stoichiometry of CD4⁺T-cell Compartments