Protein phosphatase 2A restrains DLK signaling to promote proper Drosophila synaptic development and mammalian cortical neuron survival.

ABSTRACT: Protein phosphatase 2A (PP2A) is a major cellular phosphatase with many protein substrates. As expected for a signaling molecule with many targets, inhibition of PP2A disrupts fundamental aspects of cellular physiology including cell division and survival. In post-mitotic neurons, the microtubule associated protein Tau is a particularly well-studied PP2A substrate as hyperphosphorylation of Tau is a hallmark of Alzheimer's disease. Although many cellular targets are likely altered by loss of PP2A, here we find that activation of a single pathway can explain important aspects of the PP2A loss-of-function phenotype in neurons. We demonstrate that PP2A inhibits activation of the neuronal stress kinase DLK and its Drosophila ortholog Wallenda. In the fly, PP2A inhibition activates a DLK/Wallen

SUBMITTER: Hayne M 

PROVIDER: S-EPMC9359336 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature