PIH proteins give dynein arms a hand

Long asters rock the spindle M itotic cells regulate the lengths of their astral microtubules to keep the spindle steady during cytokine-sis, Rankin and Worde-man report. Astral microtu-bules emanate from the spindle poles toward the cell cortex and help to position the cleavage furrow at the end of mitosis by confi ning actomyosin contraction to the cell equator: when microtubules are shortened with depolymer-izing drugs, contraction occurs all around the cell cortex. Rankin and Wordeman took the opposite approach to studying astral micro-tubules—lengthening them by depleting the depolymerizing motor protein MCAK or treating cells with the stabilizing drug taxol. Cytokinetic furrows formed correctly but mitotic spindles oscillated wildly between would-be daughter cells. Spindle rocking correlated with the formation of membrane blebs—protrusions at the cell poles where cortical actomyosin was disrupted. Mitotic spindles were sucked into the blebs before actin and myosin reassembled to squeeze the membrane back into shape, pushing the spindle into blebs on the opposing side. Inhibiting myosin activity stopped spindle rocking in MCAK-depleted cells. Rankin and Wordeman suggest that membrane blebs form during cytokinesis because the polar cortical cytoskeleton is weakened as actin and myosin relocate to the growing cleavage furrow. Blebbing occurs in wild-type cells too, but is particularly hazardous in the absence of MCAK because the cells' extended astral microtubules widen the blebs to a size large enough to initiate spindle oscillations. Aster size must therefore be tightly regulated to position the cleavage furrow without exacerbating membrane blebs. T he SOCS box protein SPSB2 targets inducible nitric oxide synthase (iNOS) for degradation to prevent the enzyme from damaging tissues following pathogen infection, Kuang et al. say. SOCS box proteins recruit E3 ubiquitin ligases to modify specifi c proteins and target them for destruction by the protea-some. SPSB2 is part of a subfamily of SOCS box proteins whose physiological substrates are largely unknown. Kuang et al. found that one of SPSB2's targets is iNOS, the enzyme that generates nitric oxide (NO) and other reactive nitrogen species to fi ght invading pathogens such as Leishmania major. NO is cytotoxic, so iNOS must be removed once an infection has been resolved. SPSB2 bound to iNOS and induced its ubiquitination. The enzyme was rapidly turned over by macrophages overexpressing SPSB2, whereas macrophages lacking SPSB2 degraded iNOS slowly. But the lack of SPSB2 has an upside: iNOS and NO levels were higher in SPSB2-deficient mac-rophages, allowing the cells to kill …