Interaction between the transmembrane domains of neurotrophin receptors p75 and TrkA mediates their reciprocal activation.

ABSTRACT: The neurotrophin receptors p75 and tyrosine protein kinase receptor A (TrkA) play important roles in the development and survival of the nervous system. Biochemical data suggest that p75 and TrkA reciprocally regulate the activities of each other. For instance, p75 is able to regulate the response of TrkA to lower concentrations of nerve growth factor (NGF), and TrkA promotes shedding of the extracellular domain of p75 by α-secretases in a ligand-dependent manner. The current model suggests that p75 and TrkA are regulated by means of a direct physical interaction; however, the nature of such interaction has been elusive thus far. Here, using NMR in micelles, multiscale molecular dynamics, FRET, and functional studies, we identified and characterized the direct interaction between TrkA and

SUBMITTER: Franco ML 

PROVIDER: S-EPMC8327350 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature