AIS neurofascin'd to matrix

To make a nuclear pore, just relax S taying limber is crucial not just for yoga enthusiasts, but for cells installing nuclear pores, as Scarcelli et al. report on page 799. They identify a protein that helps the passageways assemble by boosting the fl exibility of the nuclear membrane. Every molecule that enters or exits the nucleus passes through a nuclear pore complex. How cells build these channels remains murky, however. Scarcelli et al. chanced on a key contributor because of their interest in how cells export RNA from the nucleus. That process goes awry in yeast missing the protein Apq12. Cooling Apq12-lacking cells inhibited their growth, the researchers found, in part because mutant cells can’t assemble nuclear pores. Instead, many of their pore proteins, particularly those from the fi laments, clustered in the cytoplasm. Warming the cells allowed them to fashion complexes again and sent the mislocalized proteins back to become part of new pores. One way that cells cope with lower temperatures is to alter the composition of the nuclear membrane to maintain its fl exibility. Scarcelli et al. hypothesized that Apq12-defi cient yeast can’t make that adjustment. To test the idea, the researchers exposed the cells to benzyl alcohol, which slips into the membrane and loosens it up. The alcohol spurred the out-of-place pore proteins to return to their normal locations. The work indicates that Apq12’s job is to maintain membrane fl exibility. The researchers now want to determine how the protein performs that task. AIS neurofascin’d to matrix T houghts and movements depend on the axon initial segment (AIS), which instigates action potentials. On page 875, Hedstrom et al. show how a protein crucial for nerve development helps build the AIS by coating it with a layer of extracellular matrix. The AIS passes on an action potential to the nodes of Ranvier, which relay it along the rest of the axon. Although the two kinds of structures harbor almost the same molecules, they form differently. In the peripheral nervous system, neighboring Schwann cells draw the axonal protein neurofascin-186 (NF-186) to an incipient node. In turn, NF-186 lures other components, such as the cytoskeleton protein ankyrin G and sodium channels. The AIS, by contrast, assembles from its own internal signals. Studies disagree about which molecule recruits the others. To clear up the confusion, Hedstrom et al. used RNAi to eliminate AIS molecules one at a time from cultured neurons. When they knocked down ankyrin G, the other components stayed away from the AIS. However, the molecules congregated even when NF-186 or the sodium channels were missing, indicating that ankyrin G gets there fi rst. The researchers discovered that NF-186 does have an important job during AIS formation: it attracts extracellular matrix rich in the proteoglycan brevican and hooks it to the AIS. Hedstrom et al. now plan to investigate how this layer helps the AIS fi re up an action potential. Centering the centr iole L ike a sailboat, centrioles drift away if they aren’t properly moored, as Lucas and Raff show on page 725. The researchers pin down a protein that helps keep the structures in place. A pair of centrioles sits inside a cloud of pericentriolar matrix (PCM), creating the centrosome. It serves as a hub for the microtubules that form the spindle apparatus, which divvies up the chromosomes during mitosis. What connects the centrioles to the PCM and keeps them in position isn’t clear. Previous work suggested that the protein centrosomin (Cnn) attracts other proteins to the centrosome. Lucas and Raff wanted to determine whether Cnn tethered the centrioles. They started with syncytial fl y embryos, in which hundreds of dividing nuclei share a common cytoplasm. In embryos lacking Cnn, PCM still gathered at the centrioles, but the centrioles refused to stay put. Instead, they “rocketed” through the cytoplasm, trailing PCM. Microtubules powered the centrioles’ escape. These travels can foul up mitosis because the centriole often loses connection with the spindle poles. Such poles lack asters and can become entangled with neighboring spindles. Loss of Cnn had a similar effect in larval somatic cells. Centrioles strayed during mitosis, and cells sometimes ended up with extras. The work suggests that Cnn helps tie the centrioles to the PCM. The molecular mechanism is uncertain, but the researchers speculate that Cnn restrains centrioles in the middle of the centrosome by strengthening the PCM.