Abstract
Stromal interaction molecules (STIM1, 2) are acting as sensors for Ca2+ in intracellular stores and activate Orai channels at the plasma membrane for store-operated Ca2+ entry (SOCE), while classical transient receptor potential (TRPC) channel mediate receptor-operated Ca2+ entry (ROCE). Several reports, however, indicate a role for TRPC in SOCE in certain cell types. Here, we analyzed Ca2+ influx and cell function in TRPC1/6-deficient (TRPC1/6-/-) and STIM1/2- deficient (STIM1/2ΔpmLF) primary murine lung fibroblasts (pmLF). As expected, SOCE was decreased in STIM1/2- deficient pmLF and ROCE was decreased in TRPC1/6-/- pmLF compared to control cells. By contrast, SOCE was not significantly different in TRPC1/6-/- pmLF and ROCE was similar in STIM1/2-deficient pmLF compared to Wt cells. Most interestingly, cell proliferation, migration and nuclear localization of nuclear factor of activated T-cells (NFATc1 and c3) were decreased after ablation of STIM1/2 proteins in pmLF. In conclusion, TRPC1/6 channels are not involved in SOCE and STIM1/2 deficiency resulted in decreased cell proliferation and migration in pmLF.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism*
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Cell Movement* / drug effects
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cells, Cultured
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DNA / biosynthesis
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Endothelin-1 / pharmacology
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Exons / genetics
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Fibroblasts / cytology*
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Fibroblasts / metabolism*
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Integrases / metabolism
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Lung / cytology*
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Mice, Inbred C57BL
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NFATC Transcription Factors / metabolism
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ORAI1 Protein / genetics
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ORAI1 Protein / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Stromal Interaction Molecule 1 / deficiency
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Stromal Interaction Molecule 1 / genetics
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Stromal Interaction Molecule 1 / metabolism
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Stromal Interaction Molecule 2 / deficiency
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Stromal Interaction Molecule 2 / genetics
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Stromal Interaction Molecule 2 / metabolism
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Thapsigargin / pharmacology
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Transient Receptor Potential Channels / metabolism*
Substances
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Endothelin-1
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NFATC Transcription Factors
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ORAI1 Protein
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RNA, Messenger
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Stim2 protein, mouse
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Stromal Interaction Molecule 1
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Stromal Interaction Molecule 2
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Transient Receptor Potential Channels
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Thapsigargin
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DNA
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Cre recombinase
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Integrases
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Calcium