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Endocytosis and Transport of Growth Factor Receptors in Peripheral Axon Regeneration: Novel Lessons from Neurons Expressing Lysine‐Deficient FGF Receptor Type 1 in vitro

In the course of peripheral nerve regeneration, axons encounter different extracellular growth factors secreted by non‐neuronal cells at the injury site and retrogradely transported after binding to neuronal membrane receptor tyrosine kinases. The present study reviews the role of receptor transport...

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Autores principales: Hausott, Barbara, Förste, Alexandra, Zach, Fabian, Mangger, Stefan, Haugsten, Ellen Margrethe, Klimaschewski, Lars
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767123/
https://www.ncbi.nlm.nih.gov/pubmed/30950230
http://dx.doi.org/10.1002/ar.24120
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author Hausott, Barbara
Förste, Alexandra
Zach, Fabian
Mangger, Stefan
Haugsten, Ellen Margrethe
Klimaschewski, Lars
author_facet Hausott, Barbara
Förste, Alexandra
Zach, Fabian
Mangger, Stefan
Haugsten, Ellen Margrethe
Klimaschewski, Lars
author_sort Hausott, Barbara
collection PubMed
description In the course of peripheral nerve regeneration, axons encounter different extracellular growth factors secreted by non‐neuronal cells at the injury site and retrogradely transported after binding to neuronal membrane receptor tyrosine kinases. The present study reviews the role of receptor transport in peripheral axon outgrowth and provides novel data on trafficking of fibroblast growth factor receptor type 1 (FGFR1). Differences in receptor transport are determined by different numbers of lysine residues acting as ubiquitination sites in the intracellular receptor domain. We previously demonstrated that overexpression of mutant FGFR1‐25R (25 out of 29 intracellular lysines replaced with arginine) results in enhanced receptor recycling as compared to wild‐type FGFR1 followed by strong stimulation of elongative axon growth in vitro. Here, the effects of lysine‐deficient FGFR1 (FGFR1‐29R lacking all 29 cytoplasmic lysine residues) or of only 15 lysine mutations (FGFR1‐15R) on axon outgrowth and concomitant changes in signal pathway activation were investigated by immunocytochemistry and morphometry of cultured primary neurons. Overexpression of FGFR1‐15R in adult sensory neurons resulted in enhanced receptor recycling, which was accompanied by increased axon elongation without stimulating axon branching. By contrast, FGFR1‐29R was neither endocytosed nor axon outgrowth affected. Although overexpression of FGFR1‐15R or FGFR1‐25Ra strongly promoted elongation, we did not detect increased signal pathway activation (ERK, AKT, PLC, or STAT3) in neurons expressing mutant FGFR1 as compared with wild‐type neurons raising the possibility that other signaling pathways or signaling independent mechanisms may be involved in the axon outgrowth effects of recycled FGF receptors. Anat Rec, 302:1268–1275, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.
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spelling pubmed-67671232019-10-03 Endocytosis and Transport of Growth Factor Receptors in Peripheral Axon Regeneration: Novel Lessons from Neurons Expressing Lysine‐Deficient FGF Receptor Type 1 in vitro Hausott, Barbara Förste, Alexandra Zach, Fabian Mangger, Stefan Haugsten, Ellen Margrethe Klimaschewski, Lars Anat Rec (Hoboken) Thematic Papers In the course of peripheral nerve regeneration, axons encounter different extracellular growth factors secreted by non‐neuronal cells at the injury site and retrogradely transported after binding to neuronal membrane receptor tyrosine kinases. The present study reviews the role of receptor transport in peripheral axon outgrowth and provides novel data on trafficking of fibroblast growth factor receptor type 1 (FGFR1). Differences in receptor transport are determined by different numbers of lysine residues acting as ubiquitination sites in the intracellular receptor domain. We previously demonstrated that overexpression of mutant FGFR1‐25R (25 out of 29 intracellular lysines replaced with arginine) results in enhanced receptor recycling as compared to wild‐type FGFR1 followed by strong stimulation of elongative axon growth in vitro. Here, the effects of lysine‐deficient FGFR1 (FGFR1‐29R lacking all 29 cytoplasmic lysine residues) or of only 15 lysine mutations (FGFR1‐15R) on axon outgrowth and concomitant changes in signal pathway activation were investigated by immunocytochemistry and morphometry of cultured primary neurons. Overexpression of FGFR1‐15R in adult sensory neurons resulted in enhanced receptor recycling, which was accompanied by increased axon elongation without stimulating axon branching. By contrast, FGFR1‐29R was neither endocytosed nor axon outgrowth affected. Although overexpression of FGFR1‐15R or FGFR1‐25Ra strongly promoted elongation, we did not detect increased signal pathway activation (ERK, AKT, PLC, or STAT3) in neurons expressing mutant FGFR1 as compared with wild‐type neurons raising the possibility that other signaling pathways or signaling independent mechanisms may be involved in the axon outgrowth effects of recycled FGF receptors. Anat Rec, 302:1268–1275, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. John Wiley & Sons, Inc. 2019-04-22 2019-08 /pmc/articles/PMC6767123/ /pubmed/30950230 http://dx.doi.org/10.1002/ar.24120 Text en © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Thematic Papers
Hausott, Barbara
Förste, Alexandra
Zach, Fabian
Mangger, Stefan
Haugsten, Ellen Margrethe
Klimaschewski, Lars
Endocytosis and Transport of Growth Factor Receptors in Peripheral Axon Regeneration: Novel Lessons from Neurons Expressing Lysine‐Deficient FGF Receptor Type 1 in vitro
title Endocytosis and Transport of Growth Factor Receptors in Peripheral Axon Regeneration: Novel Lessons from Neurons Expressing Lysine‐Deficient FGF Receptor Type 1 in vitro
title_full Endocytosis and Transport of Growth Factor Receptors in Peripheral Axon Regeneration: Novel Lessons from Neurons Expressing Lysine‐Deficient FGF Receptor Type 1 in vitro
title_fullStr Endocytosis and Transport of Growth Factor Receptors in Peripheral Axon Regeneration: Novel Lessons from Neurons Expressing Lysine‐Deficient FGF Receptor Type 1 in vitro
title_full_unstemmed Endocytosis and Transport of Growth Factor Receptors in Peripheral Axon Regeneration: Novel Lessons from Neurons Expressing Lysine‐Deficient FGF Receptor Type 1 in vitro
title_short Endocytosis and Transport of Growth Factor Receptors in Peripheral Axon Regeneration: Novel Lessons from Neurons Expressing Lysine‐Deficient FGF Receptor Type 1 in vitro
title_sort endocytosis and transport of growth factor receptors in peripheral axon regeneration: novel lessons from neurons expressing lysine‐deficient fgf receptor type 1 in vitro
topic Thematic Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767123/
https://www.ncbi.nlm.nih.gov/pubmed/30950230
http://dx.doi.org/10.1002/ar.24120
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