Format

Send to

Choose Destination
J Cell Sci. 2016 May 1;129(9):1866-77. doi: 10.1242/jcs.184168. Epub 2016 Mar 10.

ARMS/Kidins220 and synembryn-B levels regulate NGF-mediated secretion.

Author information

1
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.
2
Institute of Biomedical Research of Salamanca (IBSAL), Salamanca 37007, Spain Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca 37007, Spain.
3
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.
4
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.

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.

KEYWORDS:

ARMS; Kidins220; NGF; Secretion; Synembryn-B; TrkA

PMID:
26966186
DOI:
10.1242/jcs.184168
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center