April 2016 | Volume 213, No. 2
People & Ideas
- PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy
In addition to recruiting Parkin/autophagy receptors to damaged mitochondria, the authors show that PINK1 triggers PKA displacement from AKAP1 after damage to trigger mitochondrial fission in a Parkin-independent manner, suggesting that PINK1 is a master mitophagy regulator.
- Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER
Heusermann et al. use a single-vesicle dye-tracing analysis in live cells showing that exosomes enter cells as intact vesicles, primarily at filopodia-active regions, and sort into endocytic vesicle circuits that are targeted to scan the ER before being directed to lysosomes.
- ZRF1 mediates remodeling of E3 ligases at DNA lesion sites during nucleotide excision repair
How ubiquitylation of multiple substrates, including repair proteins and histones, is regulated during nucleotide excision repair (NER) has been unclear. Gracheva et al. show that the histone H2A-ubiquitin binding factor ZRF1 is essential in NER as it mediates remodeling of the novel ubiquitin E3 complex responsible for monoubiquitylation of histone H2A at DNA lesion sites.
- Spindle-E cycling between nuage and cytoplasm is controlled by Qin and PIWI proteins
The mechanisms by which PIWI proteins generate piRNAs to repress expression of transposable elements in germ cells are unclear. Andress et al. examine the dynamic cycling of the RNA helicase Spindle-E with PIWI proteins and cofactors in and out of nuage granules in the Drosophila female germline and suggest that nuage granules are hubs for transient, active protein complexes associated with piRNA amplification.
- Kinesin-5 inhibitor resistance is driven by kinesin-12
The kinesin-5 Eg5 is essential for mitotic progression, and the lethal effects of Eg5 inhibitors make these inhibitors attractive candidates for chemotherapy drugs. Sturgill et al. show that kinesin-12 and a nonmotile Eg5 mutant form an alternative spindle assembly pathway that provides resistance to Eg5 inhibitors.
- Protein misfolding specifies recruitment to cytoplasmic inclusion bodies
Inclusion bodies containing aggregated disease-associated proteins and polyubiquitin conjugates are universal hallmarks of neurodegenerative diseases. Here, Bersuker et al. examine the necessity and sufficiency of ubiquitin conjugation for targeting proteins to inclusion bodies.
- Remodeling the zonula adherens in response to tension and the role of afadin in this response
During development, epithelial cells must generate and respond to tension without disrupting epithelial barrier function. The authors use superresolution microscopy in MDCK cells to examine how the zonula adherens (ZA) is remodeled in response to elevated contractility while maintain tissue integrity. They define key roles for zonula occludens family proteins in regulating contractility and for the scaffolding protein afadin in maintaining ZA architecture at tricellular junctions.
- A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion
McConnell et al. find that gradients of the repulsive guidance factor Slit induce filopodia formation and elongation toward the cue. This activity is required for axonal repulsion and is driven by ligand-induced binding of Ena/VASP proteins to the Robo receptor.
- Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotype
Ablation of the immunomodulator osteopontin correlates with reduced fibrosis and improved muscle strength in Duchenne muscular dystrophy models. Here, Capote et al. show that osteopontin ablation skews dystrophic macrophages toward a pro-regenerative phenotype, leading to improved and sustained muscle mass and strength in long-term functional testing.