Optogenetic Control of the Canonical Wnt Signaling Pathway During Xenopus laevis Embryonic Development

Vishnu V. Krishnamurthy, Hyojeong Hwang, Jia Fu, Jing Yang, Kai Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Optogenetics uses light-inducible protein-protein interactions to precisely control the timing, localization, and intensity of signaling activity. The precise spatial and temporal resolution of this emerging technology has proven extremely attractive to the study of embryonic development, a program faithfully replicated to form the same organism from a single cell. We have previously performed a comparative study for optogenetic activation of receptor tyrosine kinases, where we found that the cytoplasm-to-membrane translocation-based optogenetic systems outperform the membrane-anchored dimerization systems in activating the receptor tyrosine kinase signaling in live Xenopus embryos. Here, we determine if this engineering strategy can be generalized to other signaling pathways involving membrane-bound receptors. As a proof of concept, we demonstrate that the cytoplasm-to-membrane translocation of the low-density lipoprotein receptor-related protein-6 (LRP6), a membrane-bound coreceptor for the canonical Wnt pathway, triggers Wnt activity. Optogenetic activation of LRP6 leads to axis duplication in developing Xenopus embryos, indicating that the cytoplasm-to-membrane translocation of the membrane-bound receptor could be a generalizable strategy for the construction of optogenetic systems.

Original languageEnglish (US)
Article number167050
JournalJournal of Molecular Biology
Volume433
Issue number18
DOIs
StatePublished - Sep 2021

Keywords

  • Wnt signaling
  • Xenopus laevis
  • axis duplication
  • optogenetics

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology

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