title: Neurotrophic factors switch between two signaling pathways that trigger axonal growth.
abstract: Integration of multiple inputs from the extracellular environment, such as extracellular matrix molecules and growth factors, is a crucial process for cell function and information processing in multicellular organisms. Here we demonstrate that co-stimulation of dorsal root ganglion neurons with neurotrophic factors (NTFs) - glial-cell-line-derived neurotrophic factor, neurturin or nerve growth factor - and laminin leads to axonal growth that requires activation of Src family kinases (SFKs). A different, SFK-independent signaling pathway evokes axonal growth on laminin in the absence of the NTFs. By contrast, axonal branching is regulated by SFKs both in the presence and in the absence of NGF. We propose and experimentally verify a Boolean model of the signaling network triggered by NTFs and laminin. Our results demonstrate that NTFs provide an environmental cue that triggers a switch between separate pathways in the cell signaling network.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki FIN-00014, Finland. Mikhail.Paveliev@helsinki.fi
authors.forename: Mikhail
authors.initials: M
authors.lastname: Paveliev
authors.forename: Maria
authors.initials: M
authors.lastname: Lume
authors.forename: Agne
authors.initials: A
authors.lastname: Velthut
authors.forename: Matthew
authors.initials: M
authors.lastname: Phillips
authors.forename: Urmas
authors.initials: U
authors.lastname: Arumäe
authors.forename: Mart
authors.initials: M
authors.lastname: Saarma
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051101:Neurturin / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D007797:Laminin; D051101:Neurturin; D020932:Nerve Growth Factor; D019061:src-Family Kinases