Human CLASP1 Is an Outer Kinetochore Component that Regulates Spindle Microtubule Dynamics

Maiato, Hélder; Fairley, Elizabeth A.L.; Rieder, Conly L.; Swedlow, Jason R.; Sunkel, Cláudio E.; Earnshaw, William C.

doi:10.1016/s0092-8674(03)00465-3

Cited by 202 publications

(267 citation statements)

References 64 publications

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“…In agreement with previous studies (Maiato et al, 2003(Maiato et al, , 2005Rogers et al, 2004), we found that the flux rate was significantly decreased after RNAi treatments to deplete either Mast or KLP10A (Figure 1, A and B; Supplementary Movie 2). The extent of flux rate decrease after Mast or KLP10A RNAi (decreased 74 or 65%, respectively, relative to control rate) was comparable to the decrease measured in cells treated with low concentrations of colchicine or taxol to suppress microtubule dynamics (Supplementary Figure 2).…”

Section: Regulation Of Poleward Flux By Mast and Klp10asupporting

confidence: 92%

Poleward Tubulin Flux in Spindles: Regulation and Function in Mitotic Cells

Buster

Zhang

Sharp

2007

MBoC

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The poleward flux of tubulin subunits through spindle microtubules is a striking and conserved phenomenon whose function and molecular components remain poorly understood. To screen for novel components of the flux machinery, we utilized RNA interference to deplete regulators of microtubule dynamics, individually and in various combinations, from S2 cells and examined the resulting impact on flux rate. This led to the identification of two previously unknown flux inhibitors, KLP59C and KLP67A, and a flux promoter, Mini-spindles. Furthermore, we find that flux rate is regulated by functional antagonism among microtubule stabilizers and destabilizers specifically at plus ends. Finally, by examining mitosis on spindles in which flux has been up-or down-regulated or restored after the codepletion of antagonistic flux regulators, we show that flux is an integral contributor to anaphase A but is not responsible for chromosome congression, interkinetochore tension, or the establishment of normal spindle length during prometaphase/metaphase.

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Section: Regulation Of Poleward Flux By Mast and Klp10asupporting

confidence: 92%

Poleward Tubulin Flux in Spindles: Regulation and Function in Mitotic Cells

Buster

Zhang

Sharp

2007

MBoC

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“…It has been shown that human CLASP1 is an outer kinetochore component that regulates spindle microtubule dynamics (21). Recent studies show that improper microtubule-chromosome attachment (merotely) is a cause of chromosome missegregation in unstable cells and that increasing chromosome mis-segregation rates by elevating merotely during consecutive mitoses generates chromosome instability in otherwise stable, near-diploid cells (34,35).…”

Section: Discussionmentioning

confidence: 99%

PRC1 Cooperates with CLASP1 to Organize Central Spindle Plasticity in Mitosis

Liu

Wang

Jiang

et al. 2009

Journal of Biological Chemistry

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During cell division, chromosome segregation is governed by the interaction of spindle microtubules with the kinetochore. A dramatic remodeling of interpolar microtubules into an organized central spindle between the separating chromatids is required for the initiation and execution of cytokinesis. Central spindle organization requires mitotic kinesins, microtubulebundling protein PRC1, and Aurora B kinase complex. However, the precise role of PRC1 in central spindle organization has remained elusive. Here we show that PRC1 recruits CLASP1 to the central spindle at early anaphase onset. CLASP1 belongs to a conserved microtubule-binding protein family that mediates the stabilization of overlapping microtubules of the central spindle. PRC1 physically interacts with CLASP1 and specifies its localization to the central spindle. Repression of CLASP1 leads to sister-chromatid bridges and depolymerization of spindle midzone microtubules. Disruption of PRC1-CLASP1 interaction by a membrane-permeable peptide abrogates accurate chromosome segregation, resulting in sister chromatid bridges. These findings reveal a key role for the PRC1-CLASP1 interaction in achieving a stable anti-parallel microtubule organization essential for faithful chromosome segregation. We propose that PRC1 forms a link between stabilization of CLASP1 association with central spindle microtubules and anti-parallel microtubule elongation.

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“…Yet, little is known regarding the molecular machinery that governs the integrated coordination of various cytoskeletal components. Evidence suggests that the microtubule (MT) plus-end tracking protein CLASP [cytoplasmic linker protein (CLIP)-associated protein], which has been implicated in mitotic spindle formation (Inoue et al 2000(Inoue et al , 2004 and in linking MT ends to other cell structures such as the cell cortex and kinetochore (Akhmanova et al 2001;Maiato et al 2003;Mimori-Kiyosue et al 2005;Reis et al 2009), may play a pivotal role in the overall coordination of cytoskeletal networks. Not only does it affect MT dynamics, but CLASP may function as an actin-MT crosslinker as well, as it possesses actin-binding activity (Tsvetkov et al 2007) and CLASP-bound microtubules appear to track along F-actin bundles in growth cones (Lee et al 2004).…”

Section: Oordination Of Cytoskeletal Dynamics Is Anmentioning

confidence: 99%

Parallel Genetic and Proteomic Screens Identify Msps as a CLASP–Abl Pathway Interactor in Drosophila

Lowery

Lee²,

Lu³

et al. 2010

Genetics

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Regulation of cytoskeletal structure and dynamics is essential for multiple aspects of cellular behavior, yet there is much to learn about the molecular machinery underlying the coordination between the cytoskeleton and its effector systems. One group of proteins that regulate microtubule behavior and its interaction with other cellular components, such as actin-regulatory proteins and transport machinery, is the plus-end tracking proteins (MT1TIPs). In particular, evidence suggests that the MT1TIP, CLASP, may play a pivotal role in the coordination of microtubules with other cellular structures in multiple contexts, although the molecular mechanism by which it functions is still largely unknown. To gain deeper insight into the functional partners of CLASP, we conducted parallel genetic and proteome-wide screens for CLASP interactors in Drosophila melanogaster. We identified 36 genetic modifiers and 179 candidate physical interactors, including 13 that were identified in both data sets. Grouping interactors according to functional classifications revealed several categories, including cytoskeletal components, signaling proteins, and translation/RNA regulators. We focused our initial investigation on the MT1TIP Minispindles (Msps), identified among the cytoskeletal effectors in both genetic and proteomic screens. Here, we report that Msps is a strong modifier of CLASP and Abl in the retina. Moreover, we show that Msps functions during axon guidance and antagonizes both CLASP and Abl activity. Our data suggest a model in which CLASP and Msps converge in an antagonistic balance in the Abl signaling pathway.

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Human CLASP1 Is an Outer Kinetochore Component that Regulates Spindle Microtubule Dynamics

Cited by 202 publications

References 64 publications

Poleward Tubulin Flux in Spindles: Regulation and Function in Mitotic Cells

Poleward Tubulin Flux in Spindles: Regulation and Function in Mitotic Cells

PRC1 Cooperates with CLASP1 to Organize Central Spindle Plasticity in Mitosis

Parallel Genetic and Proteomic Screens Identify Msps as a CLASP–Abl Pathway Interactor in Drosophila

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