Isabelle Arnal1, Claire Heichette, Georgios S Diamantopoulos, Denis Chrétien. 1. Equipe Structure et Dynamique des Macromolécules, Unité Mixte de Recherche 6026, Centre National de la Recherche Scientifique, Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France. isabelle.arnal@univ-rennes1.fr
Abstract
BACKGROUND: CLIP-170 is a microtubule binding protein specifically located at microtubule plus ends, where it modulates their dynamic properties and their interactions with intracellular organelles. The mechanism by which CLIP-170 is targeted to microtubule ends remains unclear today, as well as its precise effect on microtubule dynamics. RESULTS: We used the N-terminal part of CLIP-170 (named H2), which contains the microtubule binding domains, to investigate how it modulates in vitro microtubule dynamics and structure. We found that H2 primarily promoted rescues (transitions from shrinkage to growth) of microtubules nucleated from pure tubulin and isolated centrosomes, and stimulated microtubule nucleation. Electron cryomicroscopy revealed that H2 induced the formation of tubulin rings in solution and curved oligomers at the extremities of microtubules in assembly conditions. CONCLUSIONS: These results suggest that CLIP-170 targets specifically at microtubule plus ends by copolymerizing with tubulin and modulates microtubule nucleation, polymerization, and rescues by the same basic mechanism with tubulin oligomers as intermediates.
BACKGROUND:CLIP-170 is a microtubule binding protein specifically located at microtubule plus ends, where it modulates their dynamic properties and their interactions with intracellular organelles. The mechanism by which CLIP-170 is targeted to microtubule ends remains unclear today, as well as its precise effect on microtubule dynamics. RESULTS: We used the N-terminal part of CLIP-170 (named H2), which contains the microtubule binding domains, to investigate how it modulates in vitro microtubule dynamics and structure. We found that H2 primarily promoted rescues (transitions from shrinkage to growth) of microtubules nucleated from pure tubulin and isolated centrosomes, and stimulated microtubule nucleation. Electron cryomicroscopy revealed that H2 induced the formation of tubulin rings in solution and curved oligomers at the extremities of microtubules in assembly conditions. CONCLUSIONS: These results suggest that CLIP-170 targets specifically at microtubule plus ends by copolymerizing with tubulin and modulates microtubule nucleation, polymerization, and rescues by the same basic mechanism with tubulin oligomers as intermediates.
Authors: Ram Dixit; Brian Barnett; Jacob E Lazarus; Mariko Tokito; Yale E Goldman; Erika L F Holzbaur Journal: Proc Natl Acad Sci U S A Date: 2009-01-06 Impact factor: 11.205
Authors: Kamlesh K Gupta; Benjamin A Paulson; Eric S Folker; Blake Charlebois; Alan J Hunt; Holly V Goodson Journal: J Biol Chem Date: 2008-12-13 Impact factor: 5.157
Authors: J Richard McIntosh; Ekaterina L Grishchuk; Mary K Morphew; Artem K Efremov; Kirill Zhudenkov; Vladimir A Volkov; Iain M Cheeseman; Arshad Desai; David N Mastronarde; Fazly I Ataullakhanov Journal: Cell Date: 2008-10-17 Impact factor: 41.582