Neurotrophic factors switch between two signaling pathways that trigger axonal growth.
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.
Paveliev
Mikhail
M
Institute of Biotechnology, University of Helsinki, Helsinki FIN-00014, Finland. Mikhail.Paveliev@helsinki.fi
Lume
Maria
M
Velthut
Agne
A
Phillips
Matthew
M
Arumäe
Urmas
U
Saarma
Mart
M
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
D051100:Glial Cell Line-Derived Neurotrophic Factor; D007797:Laminin; D051101:Neurturin; D020932:Nerve Growth Factor; D019061:src-Family Kinases