The Molecular Motor KIF1A Transports the TrkA Neurotrophin Receptor and Is Essential for Sensory Neuron Survival and Function

Yosuke Tanaka, Shinsuke Niwa, Ming Dong, Atena Farkhondeh, Li Wang, Ruyun Zhou, Nobutaka Hirokawa

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1215-1229
Number of pages15
JournalNeuron
Volume90
Issue number6
DOIs
Publication statusPublished - 2016 Jun 15
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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