Activation of neurotrophin signalling with light‑inducible receptor tyrosine kinases
Résumé
Optogenetics combined with protein engineering based on natural light‑sensitive dimerizing proteins has evolved as a powerful strategy to study cellular functions. The present study focused on tropomyosin kinase receptors (Trks) that have been engineered to be light‑sensitive. Trk belongs to the superfamily of receptor tyrosine kinases (RTKs), which are single‑pass transmembrane receptors that are activated by natural ligands and serve crucial roles in cellular growth, differentiation, metabolism and motility. However, functional variations exist among receptors fused with light‑sensitive proteins. The present study proposed a signal transduction model for light‑induced receptor activation. This model is based on analysis of previous light‑induced Trk receptors reported to date and comparisons to the activation mechanism of natural receptors. In this model, quantitative differences on the dimerization induced from either top‑to‑bottom or bottom‑to‑up may lead to the varying amplitude of intracellular signals. We hypothesize that the top‑to‑bottom propagation is more favourable for activation and yields better results compared with the bottom‑to‑top direction. The careful delineation of the dimerization mechanisms fine‑tuning activation will guide future design for an optimum cellular output with the precision of light.
Domaines
Biochimie, Biologie Moléculaire
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