TrkA in vivo function is negatively regulated by ubiquitination.

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2014-03-12

Author

Kiriş, Erkan
Yanpallewar, S
Dorsey, SG
Becker, J
Bavari, S
Palko, ME
Coppola, V
Tessarollo, L

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TrkA is a tyrosine kinase receptor required for development and survival of the peripheral nervous system. In the adult, TrkA and its ligand NGF are peripheral pain mediators, particularly in inflammatory pain states. However, how TrkA regulates the function of nociceptive neurons and whether its activity levels may lead to sensory abnormalities is still unclear. Here we report the characterization of a 3 aa (KFG) domain that negatively regulates TrkA level and function in response to NGF. Deletion of this domain in mouse causes a reduction of TrkA ubiquitination leading to an increase in TrkA protein levels and activity. The number of dorsal root ganglia neurons is not affected by the mutation. However, mutant mice have enhanced thermal sensitivity and inflammatory pain. Together, these data suggest that ubiquitination is a mechanism used in nociceptive neurons to regulate TrkA level and function. Our results may enhance our understanding of how ubiquitination affects TrkA activation following noxious thermal stimulation and inflammatory pain.

Subject Keywords

Nerve growth-factor, Deletion, Neurotrophins, İnternalization, Cell fate, Neuropathic pain, Endocytosis, Factor receptor trka

URI

https://hdl.handle.net/11511/41517

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

DOI

https://doi.org/10.1523/jneurosci.4294-13.2014

Collections

Department of Biology, Article

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Citation Formats

E. Kiriş et al., “TrkA in vivo function is negatively regulated by ubiquitination.,” The Journal of neuroscience : the official journal of the Society for Neuroscience, pp. 4090–8, 2014, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/41517.