2019
DOI: 10.1073/pnas.1912320116
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Optimizing photoswitchable MEK

Abstract: Optogenetic approaches are transforming quantitative studies of cell-signaling systems. A recently developed photoswitchable mitogen-activated protein kinase kinase 1 (MEK1) enzyme (psMEK) short-circuits the highly conserved Extracellular Signal-Regulated Kinase (ERK)-signaling cascade at the most proximal step of effector kinase activation. However, since this optogenetic tool relies on phosphorylation-mimicking substitutions in the activation loop of MEK, its catalytic activity is predicted to be substantial… Show more

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Cited by 33 publications
(40 citation statements)
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“…We observed retina malformations specifically in flies that were illuminated during tissue formation stages, in agreement with earlier observations that downstream pathways are not operating at maximal levels during retina development because of multiple and reiterative uses of RTKs [ 55 , 56 , 77 ]. This experiment complements recent optogenetic studies in Drosophila tissues other than the retina that have incorporated spatio-temporal regulation to identify tissues and stages with high sensitivity to ectopic signals [ 62 , 63 , 78 , 79 ].…”
Section: Discussionmentioning
confidence: 69%
See 1 more Smart Citation
“…We observed retina malformations specifically in flies that were illuminated during tissue formation stages, in agreement with earlier observations that downstream pathways are not operating at maximal levels during retina development because of multiple and reiterative uses of RTKs [ 55 , 56 , 77 ]. This experiment complements recent optogenetic studies in Drosophila tissues other than the retina that have incorporated spatio-temporal regulation to identify tissues and stages with high sensitivity to ectopic signals [ 62 , 63 , 78 , 79 ].…”
Section: Discussionmentioning
confidence: 69%
“…In a complementary experiment, we illuminated flies onwards of the second day after pupariation, which we expected to result in a reduced phenotype as this time window follows formation of the basic lattice [ 57 ]. Indeed, we did not observe large areas of disorganized tissue but rather a similar number of structures as in the unilluminated flies ( S4 Fig ), demonstrating that timed light stimulation in the earlier time window allowed targeting tissue stages that possess high sensitivity to ectopic signals [ 62 , 63 ]. The potent effects induced by Opto-dRET upon light stimulation establishes the suitability of this approach to modify tissue structure and development in vivo .…”
Section: Resultsmentioning
confidence: 84%
“…1d). The power of live imaging and biochemical assays is further extended by combining them with optogenetic perturbations of the signaling cascade that culminates in ERK activation [1214]. Here we demonstrate that datasets emerging from such varied studies (Fig.…”
Section: Figurementioning
confidence: 76%
“…We observed retina malformations specifically in flies that were illuminated during tissue formation stages, in agreement with earlier observations that downstream pathways are not operating at maximal levels during retina development because of multiple and reiterative uses of RTKs(54,55,74). This experiment complements recent optogenetic studies in Drosophila tissues other than the retina that have incorporated spatio-temporal regulation to identify tissues and stages with high sensitivity to ectopic signals(75)(76)(77)(78).We then explored if optogenetics can suppress phenotypes in a genetic model of PD.Previous optogenetic studies in the context of neurological and neurodegenerative disorders focused on understanding or correcting aberrant electrical activity in excitable cells (7, 8), whilst our goal was the delivery of trophic effects through the optical control of biochemical pro-survival pathways. Our model was Drosophila with loss of PINK1, a Ser/Thr kinase that causes autosomal recessive PD (33-35).…”
mentioning
confidence: 67%