Rme-8 depletion perturbs Notch recycling and predisposes to pathogenic signaling.

ABSTRACT: Notch signaling is a major regulator of cell fate, proliferation, and differentiation. Like other signaling pathways, its activity is strongly influenced by intracellular trafficking. Besides contributing to signal activation and down-regulation, differential fluxes between trafficking routes can cause aberrant Notch pathway activation. Investigating the function of the retromer-associated DNAJ protein Rme-8 in vivo, we demonstrate a critical role in regulating Notch receptor recycling. In the absence of Rme-8, Notch accumulated in enlarged tubulated Rab4-positive endosomes, and as a consequence, signaling was compromised. Strikingly, when the retromer component Vps26 was depleted at the same time, Notch no longer accumulated and instead was ectopically activated. Likewise, depletion of ES

SUBMITTER: Gomez-Lamarca MJ 

PROVIDER: S-EPMC4508892 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature