LIS-less neurons fall behind

IS1, the protein that is affected in the developmental disorder Lissen-cephaly, interacts with cytoplasmic dynein in several cell systems. As neuronal positioning is disrupted by this disease, LIS1 and dynein are assumed to be involved in neuronal migration. Now, live in vivo images from Tsai et al. (page 935) reveal that migration is just one facet of LIS1 function. Neuronal development was blocked at multiple stages following the loss of LIS1, probably depending on the efficiency of RNAi uptake in a cell. The earliest defect was seen in the proliferation of neural progenitors. The nuclei of these precursors normally oscillate in the neural tube and divide when they reach the ventricular surface. But nuclei of cells lacking LIS1 did not oscillate and never divided. The authors suspect that nuclear positioning dictates cell division in these precursors, perhaps via a mitosis-promoting signal at the ventricular surface. LIS1-lacking neurons also stalled at the transition to a migratory bipolar state. After mitosis, differentiating neurons work their way out L LIS1-deficient neural precursor cells (green) arrest at the nonmigratory multipolar stage in the subventricular zone. from the ventricles, but then pause and extend multiple processes, one of Formin steps and slips n page 889, Shemesh et al. suggest how formin builds actin filaments without tangling them. Formin, according to the new theory, slowly winds the filament and then undoes the twist with one big slip. Formin caps the barbed ends of actin filaments, yet allows more monomers to be added. It has been proposed that a formin dimer works as if climbing stairs. The formin dimer initially contacts the terminal actin monomers but then releases its grip on the actin monomer second from the top, allowing it to bind a new actin monomer. When that new actin monomer is added, the free half of the formin dimer attaches to it. The other half of formin then releases its actin, and so on. The model made sense but did not explain how torsion was accommodated. Each added actin mono-mer induces a slight rotation. As formin is often fixed in place at adhesion junctions, it cannot rotate. Actin O filaments attached to both formin and the cytoskeleton cannot rotate freely either. Polymerization A formin dimer (blue and green) takes several steps (left) and then changes to screw mode (right). should thus induce torsional strain and cause supercoiling, but that is not seen. Now, the authors propose …