Dynactin (red) does not get to the plus end of microtubules (green) that lack CLIP-170 (blue).

Self-love of a microtubule binding protein keeps it from its duties, according to Lansbergen et al. (page 1003).

CLIP-170 is the prototypical microtubule plus-end binding protein. It changes microtubules 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 p150Glued 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 NH2 and COOH termini. In this position, its p150Glued binding site in the COOH terminus was inaccessible. Microtubules bound to CLIP-170 at the NH2 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 p150Glued. CLIP-170 phosphorylation may regulate the microtubule binding.

Part of dynactin's job is to recruit the minus end–directed motor dynein. But being permanently stuck on a plus-end binding protein would be trouble for a motor. Release from plus ends may be brought about by LIS1. Although LIS1 is known as a dynein-associated protein, it also competed with p150Glued for binding to CLIP-170. Once LIS1 releases dynactin–dynein from CLIP-170, direct binding of dynein to microtubules may take over. Dynein could then work its way to the minus end. ▪