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Open AccessArticle

Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation

1
Division of Neuroanatomy, Medical University of Innsbruck, 6020 Innsbruck, Austria
2
Division of Histology and Embryology, Medical University of Innsbruck, 6020 Innsbruck, Austria
*
Author to whom correspondence should be addressed.
Cells 2019, 8(3), 243; https://doi.org/10.3390/cells8030243
Received: 31 January 2019 / Revised: 4 March 2019 / Accepted: 8 March 2019 / Published: 14 March 2019
(This article belongs to the Special Issue Fibroblast Growth Factor Receptor (FGFR) Signaling Pathway in Tumor)
The intracellular transport of receptor tyrosine kinases results in the differential activation of various signaling pathways. In this study, optogenetic stimulation of fibroblast growth factor receptor type 1 (FGFR1) was performed to study the effects of subcellular targeting of receptor kinases on signaling and neurite outgrowth. The catalytic domain of FGFR1 fused to the algal light-oxygen-voltage-sensing (LOV) domain was directed to different cellular compartments (plasma membrane, cytoplasm and nucleus) in human embryonic kidney (HEK293) and pheochromocytoma (PC12) cells. Blue light stimulation elevated the pERK and pPLCγ1 levels in membrane-opto-FGFR1-transfected cells similarly to ligand-induced receptor activation; however, no changes in pAKT levels were observed. PC12 cells transfected with membrane-opto-FGFR1 exhibited significantly longer neurites after light stimulation than after growth factor treatment, and significantly more neurites extended from their cell bodies. The activation of cytoplasmic FGFR1 kinase enhanced ERK signaling in HEK293 cells but not in PC12 cells and did not induce neuronal differentiation. The stimulation of FGFR1 kinase in the nucleus also did not result in signaling changes or neurite outgrowth. We conclude that FGFR1 kinase needs to be associated with membranes to induce the differentiation of PC12 cells mainly via ERK activation. View Full-Text
Keywords: optogenetics; FGF2; ERK; AKT; receptor kinase; neurite outgrowth; HEK293; PC12 optogenetics; FGF2; ERK; AKT; receptor kinase; neurite outgrowth; HEK293; PC12
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MDPI and ACS Style

Csanaky, K.; Hess, M.W.; Klimaschewski, L. Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation. Cells 2019, 8, 243.

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