A1 Refereed original research article in a scientific journal
A simple optogenetic MAPK inhibitor design reveals resonance between transcription-regulating circuitry and temporally-encoded inputs
Authors: de Mera RMMF, Li LL, Popinigis A, Cisek K, Tuittila M, Yadav L, Serva A, Courtney MJ
Publisher: NATURE PUBLISHING GROUP
Publication year: 2017
Journal: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: ARTN 15017
Volume: 8
Number of pages: 18
ISSN: 2041-1723
eISSN: 2041-1723
DOI: https://doi.org/10.1038/ncomms15017
Web address : http://www.nature.com/articles/ncomms15017
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/24961009
Engineering light-sensitive protein regulators has been a tremendous multidisciplinary challenge. Optogenetic regulators of MAPKs, central nodes of cellular regulation, have not previously been described. Here we present OptoJNKi, a light-regulated JNK inhibitor based on the AsLOV2 light-sensor domain using the ubiquitous FMN chromophore. OptoJNKi genetransfer allows optogenetic applications, whereas protein delivery allows optopharmacology. Development of OptoJNKi suggests a design principle for other optically regulated inhibitors. From this, we generate Optop38i, which inhibits p38MAPK in intact illuminated cells. Neurons are known for interpreting temporally-encoded inputs via interplay between ion channels, membrane potential and intracellular calcium. However, the consequences of temporal variation of JNK-regulating trophic inputs, potentially resulting from synaptic activity and reversible cellular protrusions, on downstream targets are unknown. Using OptoJNKi, we reveal maximal regulation of c-Jun transactivation can occur at unexpectedly slow periodicities of inhibition depending on the inhibitor's subcellular location. This provides evidence for resonance in metazoan JNK-signalling circuits.
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