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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 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 NH₂ and COOH termini. In this position, its p150^Glued 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 p150^Glued. 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 p150^Glued 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.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Related Article

Conformational changes in CLIP-170 regulate its binding to microtubules and dynactin localization

Gideon Lansbergen, Yulia Komarova, Mauro Modesti, Claire Wyman, Casper C. Hoogenraad, Holly V. Goodson, Régis P. Lemaitre, David N. Drechsel, Erik van Munster, Theodorus W.J. Gadella, Jr., Frank Grosveld, Niels Galjart, Gary G. Borisy, and Anna Akhmanova
J. Cell Biol. 2004 166: 1003-1014. [Abstract] [Full Text] [PDF]

This Article PDF (Full Text) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                      What's this?