CLIP-170 tracks growing microtubule ends by dynamically recognizing composite EB1/tubulin-binding sites

J Cell Biol. 2008 Dec 29;183(7):1223-33. doi: 10.1083/jcb.200809190. Epub 2008 Dec 22.

Abstract

The microtubule cytoskeleton is crucial for the internal organization of eukaryotic cells. Several microtubule-associated proteins link microtubules to subcellular structures. A subclass of these proteins, the plus end-binding proteins (+TIPs), selectively binds to the growing plus ends of microtubules. Here, we reconstitute a vertebrate plus end tracking system composed of the most prominent +TIPs, end-binding protein 1 (EB1) and CLIP-170, in vitro and dissect their end-tracking mechanism. We find that EB1 autonomously recognizes specific binding sites present at growing microtubule ends. In contrast, CLIP-170 does not end-track by itself but requires EB1. CLIP-170 recognizes and turns over rapidly on composite binding sites constituted by end-accumulated EB1 and tyrosinated alpha-tubulin. In contrast to its fission yeast orthologue Tip1, dynamic end tracking of CLIP-170 does not require the activity of a molecular motor. Our results demonstrate evolutionary diversity of the plus end recognition mechanism of CLIP-170 family members, whereas the autonomous end-tracking mechanism of EB family members is conserved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Humans
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Microtubules / ultrastructure*
  • Models, Biological
  • Neoplasm Proteins / metabolism*
  • Tubulin / metabolism*
  • Xenopus laevis

Substances

  • EB1 microtubule binding proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Tubulin
  • cytoplasmic linker protein 170