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• W2995932662 endingPage "318" @default.
• W2995932662 startingPage "303" @default.
• W2995932662 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 ESCRT-0 components Hrs or Stam in combination with Rme-8 also led to high levels of ectopic Notch activity. Together, these results highlight the importance of Rme-8 in coordinating normal endocytic recycling route and reveal that its absence predisposes toward conditions in which pathological Notch signaling can occur." @default.
• W2995932662 created "2019-12-26" @default.
• W2995932662 creator A5018171338 @default.
• W2995932662 creator A5018616127 @default.
• W2995932662 creator A5018777687 @default.
• W2995932662 creator A5023246606 @default.
• W2995932662 creator A5082981341 @default.
• W2995932662 date "2015-07-13" @default.
• W2995932662 modified "2023-09-26" @default.
• W2995932662 title "Rme-8 depletion perturbs Notch recycling and predisposes to pathogenic signaling" @default.
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