Optogenetic Delineation of Receptor Tyrosine Kinase Subcircuits in PC12 Cell Differentiation.

ABSTRACT: Nerve growth factor elicits signaling outcomes by interacting with both its high-affinity receptor, TrkA, and its low-affinity receptor, p75NTR. Although these two receptors can regulate distinct cellular outcomes, they both activate the extracellular-signal-regulated kinase pathway upon nerve growth factor stimulation. To delineate TrkA subcircuits in PC12 cell differentiation, we developed an optogenetic system whereby light was used to specifically activate TrkA signaling in the absence of nerve growth factor. By using tyrosine mutants of the optogenetic TrkA in combination with pathway-specific pharmacological inhibition, we find that Y490 and Y785 each contributes to PC12 cell differentiation through the extracellular-signal-regulated kinase pathway in an additive manner. Optogenetic

SUBMITTER: Khamo JS 

PROVIDER: S-EPMC7372508 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature