Protein coat keeps axons buttoned up

Jones et al. reveal how a submembranous network of cytoskeletal proteins helps maintain neuronal polarity.

The axon initial segment (AIS) is a specialized structure that, in addition to firing off action potentials, maintains neuronal polarity by preventing axonal proteins from mixing with components of the cell body and dendrites. This latter function is thought to rely on dynamic actin filaments, which could either form a dense meshwork to restrict protein diffusion or assemble into oriented tracks for myosin motors to move specific cargo in and out of the axon. Jones et al. used platinum replica electron microscopy to examine the organization of actin filaments and other AIS components.

The researchers found that actin filaments were neither dense nor oriented within the AIS structures of cultured hippocampal neurons. Instead, the segments mainly consisted of microtubule bundles surrounded by a dense coat of known AIS components such as ankyrin G and spectrin βIV. This coat looked somewhat similar to the cytoskeletal network that ankyrin and spectrin proteins form beneath the membrane of red blood cells and could represent a barrier to the diffusion of axonal membrane proteins.

The AIS did contain sparse populations of both short, stable actin filaments—which may be part of the ankyrin G–spectrin βIV coat—and slightly longer dynamic actin fibers. The latter population was dispensable for coat formation but might be required to remodel the ankyrin–spectrin network: in the presence of the actin-depolymerizing drug latrunculin B, gaps appeared in the AIS coat at sites of axon branching. Senior author Tatyana Svitkina now wants to investigate how the structure of the AIS is affected by the loss of individual coat components.