Narcissistic CLIP-170 also attracts dynactin

caffolds that hold up membrane proteins in red blood cells also support the channels needed for neuronal signaling, as shown by Lacas-Gervais et al. on page 983. Neurons fire when sodium channels clustered at the axonal initial segment (AIS) open. This depolarization is propagated by more channels clustered along axons in the Nodes of Ranvier (NR). The structure of these compartments is now shown to rely on a spectrin, relatives of which are needed for the characteristic concave shape of the red blood cell plasma membrane. The AIS and NR are rich in two spectrins: ␤ IV ⌺ 1 and S The thick scaffold beneath the NR membrane (arrow, top) is missing in neurons lacking ␤IV⌺1 spectrin (bottom). ␤ IV ⌺ 6. But loss of the ␤ IV ⌺ 1 isoform was sufficient to disrupt AIS and NR physiology. NRs in the mutants were longer and fatter and lacked the protein-dense region beneath the NR membrane, which probably corresponds to the ␤ IV ⌺ 1 scaffold. These changes interfered with membrane potential generation and propagation, thus causing deafness. Recent results showed that sodium channels are concentrated in the AIS because of both anchoring to the AIS cytoskeleton and endocytosis elsewhere. The specialized AIS cytoskeleton may prevent endocytosis at this site. In the ␤ IV ⌺ 1 mutants, the NR contained membrane protrusions that were filled with vesicular organelles. If spectrins are involved in membrane trafficking, as has been proposed, the vesicles may be a result of increased endocytosis in the mutant NR. ᭿ Narcissistic CLIP-170 also attracts dynactin elf-love of a microtubule binding protein keeps it from its duties, according to Lans-bergen et al. (page 1003). CLIP-170 is the prototypical microtubule plus-end binding protein. It changes micro-tubules dynamics by rescuing them from shrinking. Using RNAi, the authors now demonstrate that CLIP-170 is also needed to recruit dynactin to plus ends through the p150 Glued dynactin subunit. But first, CLIP-170 has to let go of itself. The authors found that CLIP-170 folds on itself through binding of its NH 2 and COOH termini. In this position, its p150 Glued binding site in the COOH terminus was inaccessible. Microtubules bound to CLIP-170 at the NH 2 terminus near the site needed for the self-interaction. Once mounted on plus ends, CLIP-170 is probably open, thus freeing its COOH terminus for binding to p150 Glued. CLIP-170 phosphorylation may regulate the microtubule binding. Part of …