Sorting of signaling receptors between membrane environments can regulate their activity. Shimizu et al. show that localization of Notch to alternative microdomains on the endosome switches between different mechanisms of activation, and lateral movement of Notch on the endosome membrane between these microdomains is regulated by Deltex and limited by differential roles of ESCRT-I and III complexes.
Using live-cell microscopy, we find that loss of VPS13C in human neurons disrupts lysosomal morphology and dynamics with increased inter-lysosomal tethers, leading to impaired lysosomal motility and defective lysosomal function as well as a decreased phospho-Rab10-mediated lysosomal stress response.
Membrane anchors of RAS play major roles in select lipid enrichment of RAS on the plasma membrane. Arora et al. show that the cytoplasmic RAS G-domains fine-tune selectivity of lipids. Their findings provide a mechanism for the allele-specific oncogenesis of KRAS4B.