Brevican (red) keeps clear of the AIS in neurons in which NF-186 is blocked (green).

Thoughts 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 first.

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 fire up an action potential.