New issue: May 17th

Today’s new issue of the JCB is full of exciting papers, so let’s get straight down to a roundup of some of the highlights…

Two papers examine how kinetochores hold on to the growing and shrinking ends of microtubules during mitosis. As the University of Washington’s Trisha Davis tells me in this week’s In Focus, “It’s pretty amazing. Thousands of subunits come off the microtubule yet the kinetochore hangs on. And when subunits are added to the microtubule end, the kinetochore stays bound to the tip.”  Davis and her collaborators (Tien et al.) along with Stefan Westermann and colleagues from the IMP in Vienna (Lampert et al.) reveal that the kinetochore accomplishes this through the coordinated activity of two microtubule-binding complexes, Ndc80 and Dam1. Both groups show that Dam1 “tracks” the dynamic tips of microtubules, pulling Ndc80 and the rest of the kinetochore with it. The aurora B kinase can disrupt the interaction between Dam1 and Ndc80, which could be a new mechanism by which the kinase eliminates incorrect kinetochore-microtubule attachments.

Elsewhere, another pair of papers examines how cells orient their mitotic spindles during epithelial cyst morphogenesis. Previous work showed that the rho GTPase Cdc42 aligns the spindle perpendicular to the apical-basal axis of the cell, so that the daughter cells' apical surfaces always end up facing the interior of the cyst, eventually forming a lumen in the center. Qin et al. perform an RNAi screen to identify guanine nucleotide exchange factors that activate Cdc42 in this process, and identify Tuba – a GEF that localizes to the cells’ apical cortex. Meanwhile, Rodriguez-Fraticelli et al. find that the centrosomally-localized Cdc42 GEF Intersectin2 also regulates spindle orientation. The image to the left shows how cysts lacking Intersectin2 (upper panel) form multiple small lumens instead of the single, large lumen formed by control cells (lower panel).

Lee et al. reveal how the ubiquitin ligase Parkin promotes the removal of defective mitochondria, and how this process goes awry in Parkinson’s disease. The researchers found that cells expressing mutant versions of Parkin failed to clear damaged mitochondria. Different Parkin mutants blocked the process at different steps: Parkin mutants lacking ubiquitin ligase activity accumulated defective mitochondria in large, peri-nuclear aggregates. Wild type Parkin cleared these aggregates by ubiquitinating the mitochondria to recruit components of the autophagy machinery leading to the organelles’ degradation. Other Parkin mutants blocked the process at earlier stages, either failing to recognize and bind damaged mitochondria, or failing to transport them along microtubules to the peri-nuclear region. Senior author Tso-Pang Yao explains here how mitochondrial degradation resembles the removal of toxic cytosolic proteins. Lee et al.’s research suggests the two processes may be linked, which is fascinating because mitochondrial dysfunction and protein aggregation are both common features of Parkinson’s disease.

Neurological disease is also caused by mutations in the transcription factor SOX10, which is required for the maintenance of neural crest stem cells and for specifying their differentiation into Schwann and other glial cells. To see if SOX10 continues to function later in development, Finzsch et al. delete the transcription factor from immature Schwann cells after their specification. Schwann cells fail to develop any further in the absence of SOX10 and lose their identity, resulting in numerous peripheral nervous system defects. For example, in wild type sciatic nerves (left), large diameter axons are individually wrapped in thick myelin sheaths. But in mutant nerves (right), a single Schwann cell surrounds multiple large and small axons.

Finally for today, Stramer et al. reveal how bundled microtubule “arms” point Drosophila macrophages in the right direction as they migrate toward wounds and help the cells repel each other when they collide. Our cover this week shows two macrophages bumping into each other in living fly embryos – the cells are spectacularly amenable to in vivo imaging, which allowed Stramer et al. to identify the bundles and determine that they require the microtubule-stabilizing protein CLASP. You can read a summary of the paper here, or you can watch the video below – the latest in our biosights series of video podcasts – where lead author Brian Stramer likens the microtubule bundles to a stiff-arm tackle in American football, allowing colliding cells to fend each other off.

Lots of other great papers in today’s new issue – you can find them all on our table of contents by clicking here.