Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation
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...
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MDPI AG
2019-03-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/8/3/243 |
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| author | Katalin Csanaky Michael W. Hess Lars Klimaschewski |
| author_facet | Katalin Csanaky Michael W. Hess Lars Klimaschewski |
| author_sort | Katalin Csanaky |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T07:38:19Z |
| format | Article |
| id | doaj.art-6e8e8e2dfb79486590275f02f9159496 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:38:19Z |
| publishDate | 2019-03-01 |
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| spelling | doaj.art-6e8e8e2dfb79486590275f02f91594962023-09-02T21:27:16ZengMDPI AGCells2073-44092019-03-018324310.3390/cells8030243cells8030243Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal DifferentiationKatalin Csanaky0Michael W. Hess1Lars Klimaschewski2Division of Neuroanatomy, Medical University of Innsbruck, 6020 Innsbruck, AustriaDivision of Histology and Embryology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDivision of Neuroanatomy, Medical University of Innsbruck, 6020 Innsbruck, AustriaThe 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.http://www.mdpi.com/2073-4409/8/3/243optogeneticsFGF2ERKAKTreceptor kinaseneurite outgrowthHEK293PC12 |
| spellingShingle | Katalin Csanaky Michael W. Hess Lars Klimaschewski Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation Cells optogenetics FGF2 ERK AKT receptor kinase neurite outgrowth HEK293 PC12 |
| title | Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation |
| title_full | Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation |
| title_fullStr | Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation |
| title_full_unstemmed | Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation |
| title_short | Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation |
| title_sort | membrane associated not cytoplasmic or nuclear fgfr1 induces neuronal differentiation |
| topic | optogenetics FGF2 ERK AKT receptor kinase neurite outgrowth HEK293 PC12 |
| url | http://www.mdpi.com/2073-4409/8/3/243 |
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