Non-canonical Ret signaling augments p75-mediated cell death in developing sympathetic neurons.

ABSTRACT: Programmed cell death (PCD) is an evolutionarily conserved process critical in sculpting many organ systems, yet the underlying mechanisms remain poorly understood. Here, we investigated the interactions of pro-survival and pro-apoptotic receptors in PCD using the sympathetic nervous system as a model. We demonstrate that Ret, a receptor tyrosine kinase required for the survival of many neuronal populations, is restricted to a subset of degenerating neurons that rapidly undergo apoptosis. Pro-apoptotic conditions induce Ret to associate with the death receptor p75. Genetic deletion of p75 within Ret⁺ neurons, and deletion of Ret during PCD, inhibit apoptosis both in vitro and in vivo. Mechanistically, Ret inhibits nerve growth factor (NGF)-mediated survival of sympathetic neuron

SUBMITTER: Donnelly CR 

PROVIDER: S-EPMC6122988 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature