Promotion of neurite outgrowth by fibroblast growth factor receptor 1 overexpression and lysosomal inhibition of receptor degradation in pheochromocytoma cells and adult sensory neurons

Neuroscience
Barbara HausottLars Klimaschewski

Abstract

Basic fibroblast growth factor (FGF-2) is up-regulated in response to a nerve lesion and promotes axonal regeneration by activation of the tyrosine kinase receptor fibroblast growth factor receptor 1 (FGFR1). To determine the effects of elevated FGFR1 levels on neurite outgrowth, overexpression was combined with lysosomal inhibition of receptor degradation. In pheochromocytoma (PC12) cells, FGFR1 overexpression resulted in flattened morphology, increased neurite outgrowth and activation of extracellular signal-regulated kinase (ERK) and AKT. Degradation of FGFR1 was inhibited by the lysosomal inhibitor leupeptin and by the proteasomal inhibitor lactacystin. In rat primary adult neurons, FGFR1 overexpression enhanced FGF-2-induced axon growth which was further increased by co-treatment with leupeptin. Lysosomal inhibition of receptor degradation concomitant with ligand stimulation of neurons overexpressing FGFR1 provides new insight in tyrosine kinase receptor-mediated promotion of axon regeneration and demonstrates that adult sensory neurons express sub-optimal levels of tyrosine kinase receptors for neurotrophic factors.

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Citations

Aug 21, 2012·Histochemistry and Cell Biology·Regina IrschickLars Klimaschewski
Jul 9, 2013·Molecular Neurobiology·Damien P Kuffler
Feb 14, 2013·Science Signaling·Malgorzata ZakrzewskaAntoni Wiedlocha
Jan 11, 2014·Neurochemical Research·Letizia MarvaldiLars Klimaschewski
Jul 30, 2015·The European Journal of Neuroscience·Barbara Hausott, Lars Klimaschewski
Nov 28, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Barbara HausottLars Klimaschewski
Jul 29, 2010·Molecular Systems Biology·William J BuchserVance P Lemmon
Mar 19, 2014·Neuroscience Letters·Thomas HausnerLars Klimaschewski
May 23, 2012·Progress in Neurobiology·Ilary AllodiXavier Navarro
Sep 20, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Soroor FarahnakJames G Martin
Apr 6, 2019·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Barbara HausottLars Klimaschewski
Nov 7, 2019·Journal of Neurology, Neurosurgery, and Psychiatry·Yannick TholanceUNKNOWN anti-FGFR3 antibody Study Group
Nov 22, 2017·World Journal of Surgery·Jenny WelanderOliver Gimm
Jun 27, 2020·International Journal of Molecular Sciences·Héctor Albert-GascóFrancisco E Olucha-Bordonau
Apr 17, 2021·Molecular Neurobiology·Lars Klimaschewski, Peter Claus

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