People & Ideas
Atypical parkinsonism–associated retromer mutant alters endosomal sorting of specific cargo proteins
Mutations in the retromer complex, which is involved in sorting integral membrane proteins from endosomes to cellular compartments, are associated with atypical parkinsonism, but how these mutations affect retromer function remains unclear. Through a quantitative proteomic analysis of the retromer interactome, McMillan et al. reveal a new mechanism for perturbed endosomal sorting in parkinsonism.
RECQ5 helicase promotes resolution of conflicts between replication and transcription in human cells
Urban et al. show that RECQ5 DNA helicase promotes RAD18-dependent PCNA ubiquitination and the processing of replication intermediates upon collisions between replication and transcription complexes.
A disulfide bond in the TIM23 complex is crucial for voltage gating and mitochondrial protein import
Here, Ramesh et al. show that import and oxidation of Tim17, a membrane-embedded subunit of the mitochondrial protein import machinery, are mediated by the mitochondrial disulfide relay, although its disulfide bond is formed differently than soluble intermembrane space proteins.
Cancer cells are critically dependent on ER–mitochondria Ca2+ flux that regulates their bioenergetics. Here, Raturi et al. identify the ER oxidoreductase TMX1 as a thiol-dependent regulator of this intracellular signaling mechanism within cancer cells.
Mutated N-Ras causes leukemia and melanoma when properly delivered to cellular membranes. Here, VPS35, a component of the retromer, is shown to carry N-Ras from one membrane compartment to another. Thus, VPS35 may be a target for anticancer drug discovery.
A Toll receptor–FoxO pathway represses Pavarotti/MKLP1 to promote microtubule dynamics in motoneurons
McLaughlin et al. uncover a motoneuronal Toll-6–directed pathway that functions via dSARM and FoxO to attenuate microtubule stability through repression of Pavarotti/MKLP1 transcription. Genetic and pharmacological strategies reveal a novel requirement for dynamic synaptic microtubules in structural plasticity, which are established by Toll-6–FoxO signaling.
ERK signaling promotes cell motility by inducing the localization of myosin 1E to lamellipodial tips
Tanimura et al. demonstrate that SH3P2 binds to and functions as a cytosolic anchor for myosin 1E (Myo1E). ERK signaling–dependent phosphorylation of SH3P2 induces the dissociation of bound Myo1E and its consequent localization to the tips of lamellipodia, where it promotes cell motility.