Optical Activation of TrkA Signaling

• DOI: 10.1021/acssynbio.8b00126
• Publication Date: 2018-07-05T21:32:56Z
• Authors: Liting Duan; Jen M. Hope; Shunling Guo; Qunxiang Ong; Amaury François; Luke Kaplan; Grégory Scherrer; Bianxiao Cui
• Keywords: Neurite; Dorsal root ganglion

Nerve growth factor/tropomyosin receptor kinase A (NGF/TrkA) signaling plays a key role in neuronal development, function, survival, and growth. The pathway is implicated neurodegenerative disorders including Alzheimer's disease, chronic pain, inflammation, cancer. NGF binds the extracellular domain of TrkA, leading to activation receptor's intracellular domain. As TrkA highly dynamic, mechanistic studies would benefit from tool with high spatial temporal resolution. Here we present design evaluation four strategies for light-inducible absence NGF. Our involve light-sensitive protein Arabidopsis cryptochrome 2 its binding partner CIB1. We demonstrate successful recapitulation native NGF/TrkA functions by optical induction plasma membrane recruitment homo-interaction TrkA. This approach activates PI3K/AKT Raf/ERK pathways, promotes neurite PC12 cells, supports survival dorsal root ganglion neurons ability activate using light bestows resolution investigating signaling.