title: CLIP-170 tracks growing microtubule ends by dynamically recognizing composite EB1/tubulin-binding sites.
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.
authors.affiliation: European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bieling
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kandels-Lewis
authors.forename: Ivo A
authors.initials: IA
authors.lastname: Telley
authors.forename: Juliette
authors.initials: J
authors.lastname: van Dijk
authors.forename: Carsten
authors.initials: C
authors.lastname: Janke
authors.forename: Thomas
authors.initials: T
authors.lastname: Surrey
mesh_terms: D000818:Animals; D001665:Binding Sites; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: C405804:EB1 microtubule binding proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D014404:Tubulin; C076744:cytoplasmic linker protein 170