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
Hauptverfasser: López-Benito, Saray, Lillo, Concepción, Hernández-Hernández, Ángel, Chao, Moses V, Arévalo, Juan C
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container_end_page 1877
container_issue 9
container_start_page 1866
container_title Journal of cell science
container_volume 129
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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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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