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The Molecular Motor KIF1A Transports the TrkA Neurotrophin Receptor and Is Essential for Sensory Neuron Survival and Function.
- Source :
-
Neuron [Neuron] 2016 Jun 15; Vol. 90 (6), pp. 1215-1229. Date of Electronic Publication: 2016 Jun 02. - Publication Year :
- 2016
-
Abstract
- KIF1A is a major axonal transport motor protein, but its functional significance remains elusive. Here we show that KIF1A-haploinsufficient mice developed sensory neuropathy. We found progressive loss of TrkA(+) sensory neurons in Kif1a(+/-) dorsal root ganglia (DRGs). Moreover, axonal transport of TrkA was significantly disrupted in Kif1a(+/-) neurons. Live imaging and immunoprecipitation assays revealed that KIF1A bound to TrkA-containing vesicles through the adaptor GTP-Rab3, suggesting that TrkA is a cargo of the KIF1A motor. Physiological measurements revealed a weaker capsaicin response in Kif1a(+/-) DRG neurons. Moreover, these neurons were hyposensitive to nerve growth factor, which could explain the reduced neuronal survival and the functional deficiency of the pain receptor TRPV1. Because phosphatidylinositol 3-kinase (PI3K) signaling significantly rescued these phenotypes and also increased Kif1a mRNA, we propose that KIF1A is essential for the survival and function of sensory neurons because of the TrkA transport and its synergistic support of the NGF/TrkA/PI3K signaling pathway.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Capsaicin pharmacology
Cell Survival
Gene Knockdown Techniques
Kinesins genetics
Kinesins metabolism
Mice
Nerve Growth Factor pharmacology
Nociceptors drug effects
Nociceptors metabolism
Nociceptors physiology
Phosphatidylinositol 3-Kinases metabolism
Axonal Transport physiology
Ganglia, Spinal metabolism
Kinesins physiology
Receptor, trkA metabolism
Sensory Receptor Cells physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 90
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 27263974
- Full Text :
- https://doi.org/10.1016/j.neuron.2016.05.002