RhoGDI phosphorylation by PKC promotes its interaction with death receptor p75NTR to gate axon...

ABSTRACT: How receptors juggle their interactions with multiple downstream effectors remains poorly understood. Here we show that the outcome of death receptor p75NTR signaling is determined through competition of effectors for interaction with its intracellular domain, in turn dictated by the nature of the ligand. While NGF induces release of RhoGDI through recruitment of RIP2, thus decreasing RhoA activity in favor of NFkB signaling, MAG induces PKC-mediated phosphorylation of the RhoGDI N-terminus, promoting its interaction with the juxtamembrane domain of p75NTR, disengaging RIP2, and enhancing RhoA activity in detriment of NF-kB. This results in stunted neurite outgrowth and apoptosis in cerebellar granule neurons. If presented simultaneously, MAG prevails over NGF. The NMR solution structure o

SUBMITTER: Dr. Ajeena Ramanujan 

PROVIDER: S-SCDT-10_1038-S44319-024-00064-2 | biostudies-other |

REPOSITORIES: biostudies-other