title: ARMS/Kidins220 and synembryn-B levels regulate NGF-mediated secretion.
abstract: Proper development of the nervous system requires a temporally and spatially orchestrated set of events including differentiation, synapse formation and neurotransmission. Nerve growth factor (NGF) acting through the TrkA neurotrophin receptor (also known as NTRK1) regulates many of these events. However, the molecular mechanisms responsible for NGF-regulated secretion are not completely understood. Here, we describe a new signaling pathway involving TrkA, ARMS (also known as Kidins220), synembryn-B and Rac1 in NGF-mediated secretion in PC12 cells. Whereas overexpression of ARMS blocked NGF-mediated secretion, without affecting basal secretion, a decrease in ARMS resulted in potentiation. Similar effects were observed with synembryn-B, a protein that interacts directly with ARMS. Downstream of ARMS and synembryn-B are Gαq and Trio proteins, which modulate the activity of Rac1 in response to NGF. Expression of dominant-negative Rac1 rescued the secretion defects of cells overexpressing ARMS or synembryn-B. Thus, this neurotrophin pathway represents a new mechanism responsible for NGF-regulated secretion.
authors.affiliation: Department of Cell Biology and Pathology, Instituto de Neurociencias de Castilla y León (INCyL), University of Salamanca, Salamanca 37007, Spain Institute of Biomedical Research of Salamanca (IBSAL), Salamanca 37007, Spain.
authors.forename: Saray
authors.initials: S
authors.lastname: López-Benito
authors.affiliation: Department of Cell Biology and Pathology, Instituto de Neurociencias de Castilla y León (INCyL), University of Salamanca, Salamanca 37007, Spain Institute of Biomedical Research of Salamanca (IBSAL), Salamanca 37007, Spain.
authors.forename: Concepción
authors.identifier: 0000-0001-5814-9826
authors.initials: C
authors.lastname: Lillo
authors.affiliation: Institute of Biomedical Research of Salamanca (IBSAL), Salamanca 37007, Spain Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca 37007, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Hernández-Hernández
authors.affiliation: Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, Departments of Cell Biology, Physiology and Neuroscience, Psychiatry, and Neural Sciences, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Moses V
authors.initials: MV
authors.lastname: Chao
authors.affiliation: Department of Cell Biology and Pathology, Instituto de Neurociencias de Castilla y León (INCyL), University of Salamanca, Salamanca 37007, Spain Institute of Biomedical Research of Salamanca (IBSAL), Salamanca 37007, Spain arevalojc@usal.es.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Arévalo
mesh_terms: D000818:Animals; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C482591:KIDINS220 protein, human; C418610:Kidins220 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C107953:RAC1 protein, human; C485885:Ric8a protein, rat; D020932:Nerve Growth Factor; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein
keywords: ARMS; Kidins220; NGF; Secretion; Synembryn-B; TrkA