ARMS/Kidins220 and synembryn-B levels regulate NGF-mediated secretion
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. Ho...
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Veröffentlicht in: | Journal of cell science 2016-05, Vol.129 (9), p.1866-1877 |
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container_title | Journal of cell science |
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creator | López-Benito, Saray Lillo, Concepción Hernández-Hernández, Ángel Chao, Moses V Arévalo, Juan C |
description | 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. |
doi_str_mv | 10.1242/jcs.184168 |
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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.</description><identifier>ISSN: 0021-9533</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.184168</identifier><identifier>PMID: 26966186</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Guanine Nucleotide Exchange Factors - genetics ; Guanine Nucleotide Exchange Factors - metabolism ; HEK293 Cells ; Humans ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; Nerve Growth Factor - genetics ; Nerve Growth Factor - secretion ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; PC12 Cells ; Phosphoproteins - genetics ; Phosphoproteins - metabolism ; rac1 GTP-Binding Protein - genetics ; rac1 GTP-Binding Protein - metabolism ; Rats</subject><ispartof>Journal of cell science, 2016-05, Vol.129 (9), p.1866-1877</ispartof><rights>2016. 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subjects | Animals Guanine Nucleotide Exchange Factors - genetics Guanine Nucleotide Exchange Factors - metabolism HEK293 Cells Humans Membrane Proteins - genetics Membrane Proteins - metabolism Mice Nerve Growth Factor - genetics Nerve Growth Factor - secretion Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Nuclear Proteins - genetics Nuclear Proteins - metabolism PC12 Cells Phosphoproteins - genetics Phosphoproteins - metabolism rac1 GTP-Binding Protein - genetics rac1 GTP-Binding Protein - metabolism Rats |
title | ARMS/Kidins220 and synembryn-B levels regulate NGF-mediated secretion |
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