Contrasts in neuronal aggregates

he protein aggregates of various neuro-degenerative diseases are not created equal. So say Matsumoto et al. (page 75), who find that the aggregates of familial amyo-trophic lateral sclerosis (fALS) are unusually porous compared to those of Huntington's disease (HD). Both diseases are associated with the neuronal aggregation of a mutant protein in affected individuals. For fALS, the mutant protein is the free radical scavenger SOD1. The authors found that, unlike mutant htt, which forms a solid, impenetrable aggregate in HD, mutant SOD1 formed a honeycomb like structure. YFP and other globular proteins were able to diffuse freely through cells containing SOD1 aggregates. Certain proteins were not as free to come and go, however. These proteins might thus be the basis for cellular toxicity. The proteasome, a known interacting partner for many neurodegener-ative disease–associated proteins, was trapped by the SOD1 aggregates, as it is by htt aggregates. Proteasomal activity was thus stymied. T Breaking cell bonds ell–cell junctions are pulled apart by cytoskeletal traction forces during epithelial cell scattering. The results from De Rooij et al. (page 153) suggest that down-regulation of the cell–cell glue, E-cadherin, is not required in this process. During cell scattering induced by hepatocyte growth factor (HGF), cell contacts must necessarily be disrupted. The down–regulation of E-cadherin expression or function by HGF has thus been the focus of attention for researchers interested in how epithelial cells acquire migratory abilities. Now, the new findings indicate that cadherins remain functional but are forcibly ripped apart. C HGF-treated cells that did not migrate away from their neighbors maintained functional E-cadherin adhesions. New adhesions were also built as scattering cells made new encounters. Though working properly, E-cadherin adhesions were rapidly lost just as cells started migrating. According to the authors, the cell–cell junctions are pulled apart by forces stemming from cell–matrix adhesions. Thick actin bundles were seen between matrix-attached focal adhesions in distant parts of the cell and those adjacent to cadherin-based junctions. Active myosin, which contracts actin fibers, localized along these bundles upon HGF treatment. Strong integrin-based adhesions to collagen and fibronectin supported fast, efficient scattering. The weaker bonds of laminin were less efficient in inducing scattering, even though laminin supported the fastest migration velocity. Some tension is required to maintain cell–cell adhesions, but clearly too much can be their downfall. The authors are thus curious to know how adhesions measure tension levels and how E-cadherin junctions are pulled apart. …