title: CLIP-170 facilitates the formation of kinetochore-microtubule attachments.
abstract: CLIP-170 is a microtubule 'plus end tracking' protein involved in several microtubule-dependent processes in interphase. At the onset of mitosis, CLIP-170 localizes to kinetochores, but at metaphase, it is no longer detectable at kinetochores. Although RNA interference (RNAi) experiments have suggested an essential role for CLIP-170 during mitosis, the molecular function of CLIP-170 in mitosis has not yet been revealed. Here, we used a combination of high-resolution microscopy and RNAi-mediated depletion to study the function of CLIP-170 in mitosis. We found that CLIP-170 dynamically localizes to the outer most part of unattached kinetochores and to the ends of growing microtubules. In addition, we provide evidence that a pool of CLIP-170 is transported along kinetochore-microtubules by the dynein/dynactin complex. Interference with CLIP-170 expression results in defective chromosome congression and diminished kinetochore-microtubule attachments, but does not detectibly affect microtubule dynamics or kinetochore-microtubule stability. Taken together, our results indicate that CLIP-170 facilitates the formation of kinetochore-microtubule attachments, possibly through direct capture of microtubules at the kinetochore.
authors.affiliation: Division of Molecular Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Tanenbaum
authors.forename: Niels
authors.initials: N
authors.lastname: Galjart
authors.forename: Marcel A T M
authors.initials: MA
authors.lastname: van Vugt
authors.forename: René H
authors.initials: RH
authors.lastname: Medema
mesh_terms: D002478:Cells, Cultured; D002875:Chromosomes / Q000378:metabolism; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000737:chemistry / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D008938:Mitosis; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D008941:Spindle Apparatus / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C076744:cytoplasmic linker protein 170; D004398:Dyneins