Arf1 doubles up to release vesicles

A n HIV-1 protein promotes chromosome missegrega-tion by epigenetically modifying centromeric chromatin, Shimura et al. report. Lymphocytes infected with HIV-1 display premature chromatid separation (PCS), in which sister chro-matids come apart too early in mitosis, increasing the possibility of missegregation into the wrong daughter cell. This genomic instability may explain the increased incidences of certain cancers in HIV-1 patients, though how HIV-1 induces PCS is unknown. Shimura et al. found that viruses lacking the small accessory gene vpr didn't disrupt chromatid cohesion, whereas expression of Vpr alone was suffi cient to induce PCS. Cohesin proteins, which link sister chromatids together until anaphase, were prematurely lost from the centromeres of mitotic chromosomes, probably because hSgo1, a protein that protects cohesins from dissociation, was displaced in the presence of Vpr. hSgo1 is recruited to centromeres by heterochromatin proteins of the HP1 family. Shimura et al. saw that HP1-␣ and HP1-␥ were displaced from centromeric chromatin by Vpr and that depleting HP1 proteins by RNAi caused similar levels of PCS. Vpr localized to chromosomes—especially at centromeres—and displaced HP1-␣ and-␥ by recruiting the histone acetyltransferase p300 to modify the surrounding chromatin. Depleting or inhibiting p300 prevented Vpr from displacing HP1 proteins and inducing PCS. Blocking the interaction between Vpr and p300 may therefore reduce genomic instability in long-term HIV-1 patients. Senior author Mari Shimura now wants to investigate how the Vpr protein localizes to host cell chromosomes. S engupta Ghosh et al. describe how the kinase DLK activates a specifi c pool of JNK molecules to promote neu-ronal degeneration during development. Developing sensory neurons compete for nerve growth factor (NGF); the losing cells die or retract their axons, thereby refi ning the innervation of peripheral targets. Sengupta Ghosh et al. generated mice lacking the mixed lineage kinase DLK and found that cell death was reduced in the peripherally projecting neurons of these animals. Dorsal root ganglion neurons isolated from DLK-null mice grew normally but were protected from axon degeneration and apoptosis after NGF withdrawal. The researchers looked for signaling pathways altered in DLK-null neurons and found that, in the absence of DLK, NGF withdrawal failed to stimulate JNK, a MAP kinase that promotes neuronal degeneration. Yet basal levels of JNK activity— essential for normal neuronal function—remained unchanged in DLK-null neurons, indicating that DLK activates a subset of JNK molecules after NGF removal. DLK bound to JIP3, a scaffold protein that also interacts with JNK. …