Acute and chronic effects of a light-activated FGF receptor in keratinocytes in vitro and in mice

Theresa Rauschendorfer, Selina Gurri, Irina Heggli, Luigi Maddaluno, Michael Meyer, Álvaro Inglés-Prieto, Harald Janovjak, Sabine Werner

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
6 Downloads (Pure)

Abstract

FGFs and their high-affinity receptors (FGFRs) play key roles in development, tissue repair, and disease. Because FGFRs bind overlapping sets of ligands, their individual functions cannot be determined using ligand stimulation. Here, we generated a light-activated FGFR2 variant (OptoR2) to selectively activate signaling by the major FGFR in keratinocytes. Illumination of OptoR2-expressing HEK 293T cells activated FGFR signaling with remarkable temporal precision and promoted cell migration and proliferation. In murine and human keratinocytes, OptoR2 activation rapidly induced the classical FGFR signaling pathways and expression of FGF target genes. Surprisingly, multi-level counter-regulation occurred in keratinocytes in vitro and in transgenic mice in vivo, including OptoR2 down-regulation and loss of responsiveness to light activation. These results demonstrate unexpected cell type–specific limitations of optogenetic FGFRs in long-term in vitro and in vivo settings and highlight the complex consequences of transferring optogenetic cell signaling tools into their relevant cellular contexts.

Original languageEnglish
Article numbere202101100
Number of pages12
JournalLife Science Alliance
Volume4
Issue number11
DOIs
Publication statusPublished - Nov 2021
Externally publishedYes

Keywords

  • light-activated FGF
  • keratinocytes
  • chronic

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