People & Ideas
Lammerding and Wolf discuss recent advances in our understanding of the mechanisms controlling transient nuclear envelope ruptures in vitro.
Huang and Rasband discuss Albrecht et al.’s new model for the axon initial segment’s diffusion barrier.
Philipp Niethammer highlights work from the Rottapel group exploring the role of the GEF-H1 protein in shear- sensing by neutrophils.
Hatch and Hetzer show that nuclear envelope rupture in cancer cells is caused by defects in lamina organization, resulting in an increase in intranuclear pressure from actin-based nucleus confinement.
A diffusion barrier impeding membrane molecule motion between the axon and the somatodendritic compartment develops as neurons mature and the axon initial segment (AIS) is enriched in specific molecules. Albrecht et al. analyze the mobility of lipid-anchored molecules in the AIS using single-particle tracking time course experiments and propose a new mechanistic model for the AIS diffusion barrier.
Using a tongue-inspired in vitro platform, Nesmith et al. demonstrate that DMD myoblasts fail to align and polarize with respect to extracellular matrix cues in the same manner as healthy myoblasts, resulting in diminished myotube formation and weaker contractile strength.
Passive macromolecular diffusion through nuclear pore complexes is thought to decrease dramatically beyond ∼40 kD. Using time-resolved fluorescence microscopy and Brownian dynamics simulations, Timney et al. show that this barrier is in fact much softer, decreasing along a continuum.
The Ska complex is crucial for kinetochore–microtubule stability and is a substrate of Aurora B, master regulator of kinetochore–microtubule attachment dynamics. Here, Redli et al. show that Ska promotes Aurora B activity to limit its own microtubule and kinetochore association and ensure proper chromosome biorientation and segregation.
Uematsu et al. show that ASB7 ubiquitinates DDA3, which facilitates Kif2a-mediated depolymerization of microtubules (MTs) for proteasomal degradation. The presence of MTs prevents the ASB7–DDA3 interaction, suggesting a feedback loop to appropriately regulate MT polymerization and spindle dynamics.
In their work, Fine et al. demonstrate that GEF-H1 is required for the spreading and crawling of neutrophils in response to intravascular blood flow. They uncover a novel mechanism that couples shear stress with Rho-dependent migratory behavior of neutrophils during inflammation.
Kunii et al. reveal that the SNARE protein SNAP23 plays distinct roles in the secretion of amylase in exocrine cells and of insulin in endocrine cells the pancreas and show that MF286, a novel inhibitor of SNAP23, may be a new drug candidate for diabetes.