On the cover
Vectorial rendered, 3D reconstruction of natural killer cells among K562 target cells imaged by 3D-SIM. The centrosome is revealed in blue by the immunodetection of pericentrin, the actin cytoskeleton is visible in green, and the natural killer cells are identifiable by the presence of lytic granules stained in red. Hsu et al. reveal that natural killer cells converge lytic granules to improve the efficiency of targeted killing and prevent collateral damage to neighboring cells. Image generated by Alexandre Carisey and Malini Mukherjee. Image © 2016 Hsu et al.
See page 875.
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People & Ideas
Da Silva and Jantsch discuss work by Lawrence et al. demonstrating a link between the nucleus and cytoplasm for DNA repair.
Zhao and Zhang discuss a new study by Nazio et al. that demonstrates that NEDD4L and mTOR regulate autophagy via modulation of ULK1 levels.
Martens previews work by Nguyen et al. analyzing the essential functions of ATG8 family proteins LC3/GABARAPs in autophagy.
Ritter and Mellman highlight work by Hsu et al. exploring the role of lytic granule convergence in targeted killing by NK cells.
In this review, Gomez-Navarro and Miller summarize the principles of cargo sorting by the vesicle traffic machinery and consider the diverse mechanisms by which cargo proteins are selected and captured into different transport vesicles.
Calcium channel regulator Mid1 links TORC2-mediated changes in mitochondrial respiration to autophagy
Rapamycin-insensitive TORC2 signaling promotes amino acid starvation–induced autophagy through inhibition of the calcium-dependent phosphatase calcineurin. Vlahakis et al. show that this regulation requires the ER calcium channel regulatory protein Mid1, which couples mitochondrial ROS accumulation in TORC2 mutants to calcineurin activation and autophagy repression.
Using laser microsurgery, Silva et al. show that gaps in the contractile ring can be repaired at any stage of constriction, allowing for successful and timely cytokinesis. Their results support a contractile unit model for constriction of the cytokinetic ring.
LINC complexes promote homologous recombination in part through inhibition of nonhomologous end joining
DNA repair is critical for genome integrity. Lawrence et al. reveal a role for a novel complex that links the nucleus to microtubules to promote accurate repair through both inhibition of error-prone nonhomologous end joining and promotion of homologous recombination.
MOZART1 and γ-tubulin complex receptors are both required to turn γ-TuSC into an active microtubule nucleation template
Cells use γ-tubulin complex to nucleate microtubules. The assembly of active microtubule nucleator is spatially and temporally regulated through the cell cycle. Lin et al. show that the protein Mzt1/MOZART1 and γ-tubulin complex receptors directly interact and act together to assemble the γ-tubulin small complex into an active microtubule nucleation template and that such interaction is conserved between Candida albicans and human cells.
ULK1 is a key kinase in autophagy initiation. Nazio et al. demonstrate that the E3 ubiquitin ligase NEDD4L targets ULK1 for degradation soon after autophagy induction, whereas a simultaneous ULK1 mRNA transcription is needed for priming subsequent rounds of autophagy.
Atg8 family LC3/GABARAP proteins are crucial for autophagosome–lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation
Current autophagy models suggest that Atg8 family LC3/GABARAP proteins are essential mediators of autophagosome biogenesis. Nguyen et al. exploit CRISPR/Cas9-generated knockouts of the LC3 or GABARAP subfamilies, or both subfamilies, to show that Atg8s are dispensable for autophagosome biogenesis but essential for autophagosome–lysosome fusion.
Lytic granule convergence to the MTOC prepares NK cells for cytotoxic effector function. Hsu et al. demonstrate that convergence increases specificity in directed secretion, thereby preventing bystander killing.