Rab27a builds a platform for HIV-1

O'Regan et al. reveal that the mitotic kinase Nek6 targets the chaperone Hsp72 to the mitotic spindle, where it promotes the formation of stable K-fi bers. Nek6 is required for robust spindle assembly and mitotic progression, but its substrates are largely unknown. O'Regan et al. found that the kinase bound to Hsp72 and, during mitosis, phosphory-lated a conserved threonine residue in the chaperone's nucleotide-binding domain. This promoted Hsp72 recruitment to the mitotic spindle. Knocking down the chaperone caused mitotic HeLa cells to form fewer K-fi bers, stable microtubule bundles that connect chromosomes to the spindle poles. As a result, chromosomes often failed to congress at the cell equator during metaphase or failed to stay there once they had arrived, thus delaying anaphase onset. Hsp72 promoted the interaction between ch-TOG and TACC3, which crosslink K-fi ber microtubules. Both proteins were lost from mitotic spindles in the absence of either Hsp72 or Nek6, but a phos-phomimetic version of Hsp72 rescued ch-TOG/TACC3 localization, K-fi ber formation, and mitotic progression in Nek6-defi cient cells. Hsp72 and related chaperones are often overexpressed in human tumors, and cancer cells that frequently contain aneuploid genomes and amplifi ed centrosomes are particularly sensitive to mitotic spindle defects. Hsp72 and/or Nek6 could therefore be attractive therapeutic targets to inhibit spindle assembly and cancer cell division. Senior author Andrew Fry now wants to investigate how Nek6 phos-phorylation targets Hsp72 to the spindle. Elsewhere in this issue, Fry, together with Suzanna Prosser and colleagues, demonstrate that the related kinase Nek5 regulates the timing of centrosome separation, another process that orchestrates spindle assembly in mitosis. Autophagosomes gain the dynein motor complexes they need to move away from axonal terminals by fusing with late endosomes, Cheng et al. reveal. During autophagy, auto-phagosomes engulf cyto-plasmic components and deliver them to lysosomes for degradation. In neurons, mature acidic lysosomes are enriched in the cell body, so autophagosomes formed at the distal ends of axons must be transported back to the soma by the motor protein dynein. How dynein is recruited to autophagosomes is unknown, however. Cheng et al. found that the majority of axonal autophagosomes fuse with late endosomes to form intermediate organelles known as amphisomes. Unlike autophagosomes, but similar to late endosomes, amphisomes were associated with dynein and moved along axons toward the cell body. This suggested that autophagosomes might become mobile by fusing with late endosomes and sharing their complement of dynein motors. …