Autophagy inhibitors deliver a knock-out blow

Airport security checkpoints might take a lesson from the nuclear pore complex (NPC), where, according to Dange et al., there are no long lines and no slowdown despite the hubbub around them. The group used single-molecule video microscopy, with a localization precision of about the width of a protein, to track single molecules of labeled, cargo-carrying receptors entering the NPC in vivo. They had previously used the same technique to look at the NPC in lifeless cells, but thought that the lack of vital activity—the absence of ion gradients in the cytoplasm, transcription in the nucleus— might affect the receptor's behavior. Instead, they found that the spatial and temporal details of NPC transport for the three receptors they studied was essentially the same: Once a receptor encountered the NPC, it was largely confi ned to a narrow central channel, and moved quickly through the pore to deliver its cargo. " There was no waiting at the gate, " says corresponding author David Grünwald. The similarity between their in vivo data and their previous experiments suggests that nuclear import dynamics are determined mainly by cargo–receptor–pore interactions, and are mostly free of infl uence from other cell processes and other transported molecules, including, surprisingly, RNA. Grünwald suggests that perhaps RNA has its own export pathway through the NPC, a possibility the team intends to study in the future. Dividing cells aren't quite as obsessed with quality control as previously thought, according to results from O'Connell and colleagues. The spindle assembly checkpoint assures that chromosomes segregate properly during mitosis. This checkpoint has been thought to monitor two separate events: the attachment of kinetochores to spindle fi bers, and the stretch force across the centromere as paired sister chromatid kinetochores start to pull apart. But whether detection of stretch is required to satisfy the checkpoint has never been conclusively demonstrated. To test this, the authors treated cells with hydroxyurea to inhibit replication, creating cells that undergo mitosis with unreplicated genomes (MUG). Such cells contain normal centrosomes and form bipolar spindles, but each kinetochore is unreplicated; thus, inner centromere stretch is not possible. MUG cells weren't normal in every respect—their kinetochores were separated from the bulk of chromatin, unattached chromatin was largely excluded from the spindle apparatus, and the duration of mitosis was more variable and longer on average than in normal cells. Nonetheless, a normal bipolar spindle formed, and kinetochores attached to spindle microtubules, …