title: Dynamic response diversity of NFAT isoforms in individual living cells.
abstract: Processing of external information by mammalian cells often involves seemingly redundant isoforms of signaling molecules and transcription factors. Understanding the functional relevance of coexpressed isoforms that respond to the same signal and control a shared set of genes is still limited. Here we show, using imaging of individual living mammalian cells, that the closely related transcription factors NFAT1 and NFAT4 possess distinct nuclear localization dynamics in response to cell stimulation. NFAT4 shows a fast response, with rapid stochastic bursts of nuclear localization. Burst frequency grows with signal level, while response amplitude is fixed. In contrast, NFAT1 has a slow, continuous response, and its amplitude increases with signal level. These diverse dynamical features observed for single cells are translated into different impulse response strategies at the cell population level. We suggest that dynamic response diversity of seemingly redundant genes can provide cells with enhanced capabilities of temporal information processing.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Nissan
authors.initials: N
authors.lastname: Yissachar
authors.forename: Tali
authors.initials: T
authors.lastname: Sharar Fischler
authors.forename: Ariel A
authors.initials: AA
authors.lastname: Cohen
authors.forename: Shlomit
authors.initials: S
authors.lastname: Reich-Zeliger
authors.forename: Dor
authors.initials: D
authors.lastname: Russ
authors.forename: Eric
authors.initials: E
authors.lastname: Shifrut
authors.forename: Ziv
authors.initials: Z
authors.lastname: Porat
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D029721:Drosophila Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D007073:Immunoglobulin E / Q000502:physiology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D050778:NFATC Transcription Factors / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D059010:Single-Cell Analysis; D059008:Time-Lapse Imaging
chemical_list: D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D050778:NFATC Transcription Factors; D020033:Protein Isoforms; C407307:chb protein, Drosophila; D007073:Immunoglobulin E; D002118:Calcium