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In polarized cells or cells with complex geometry, clustering of plasma-membrane (PM) ion channels is an effective mechanism for eliciting spatially restricted signals. However, channel clustering is also seen in cells with relatively simple topology, suggesting it fulfills a more fundamental role in cell biology than simply orchestrating compartmentalized responses. Here, we have compared the ability of store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels confined to PM microdomains with a similar number of dispersed CRAC channels to activate transcription factors, which subsequently increase nuclear gene expression. For similar levels of channel activity, we find that channel confinement is considerably more effective in stimulating gene expression. Our results identify a long-range signaling advantage to the tight evolutionary conservation of channel clustering and reveal that CRAC channel aggregation increases the strength, fidelity, and reliability of the general process of excitation-transcription coupling.

Original publication




Journal article


Cell Rep

Publication Date





203 - 216


Animals, Calcium, Calcium Channels, Cell Line, Cell Membrane, Gene Expression, Genes, Reporter, HEK293 Cells, Humans, Membrane Microdomains, Microscopy, Confocal, Mutagenesis, Site-Directed, NFATC Transcription Factors, ORAI1 Protein, Proto-Oncogene Proteins c-fos, RNA Interference, RNA, Small Interfering, Rats, Real-Time Polymerase Chain Reaction, Signal Transduction