SnapShot: Motor Proteins in Spindle Assembly

Loughlin, Rose; Riggs, Blake; Heald, Rebecca

doi:10.1016/j.cell.2008.07.038

Cited by 13 publications

(8 citation statements)

References 10 publications

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“…This process depends upon the action of a bipolar, macromolecular machine, the mitotic spindle, which uses dynamic microtubules (MTs) plus multiple kinesin and dynein motors to generate the piconewton-scale forces required for mitotic movements (Loughlin et al, 2008; Goshima and Scholey, 2010; Walczak et al, 2010; McIntosh et al, 2012). Of these, the MT-based motor, Kinesin-5 plays a key role, being essential for the assembly of bipolar spindles in most eukaryotic cells and driving or constraining the rate of spindle elongation (Enos and Morris, 1990; Sawin et al, 1992; Saunders et al, 2007; Brust-Mascher et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Structural basis for the assembly of the mitotic motor Kinesin-5 into bipolar tetramers

Nithianantham

Scholey

Al-Bassam

2014

eLife

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Chromosome segregation during mitosis depends upon Kinesin-5 motors, which display a conserved, bipolar homotetrameric organization consisting of two motor dimers at opposite ends of a central rod. Kinesin-5 motors crosslink adjacent microtubules to drive or constrain their sliding apart, but the structural basis of their organization is unknown. In this study, we report the atomic structure of the bipolar assembly (BASS) domain that directs four Kinesin-5 subunits to form a bipolar minifilament. BASS is a novel 26-nm four-helix bundle, consisting of two anti-parallel coiled-coils at its center, stabilized by alternating hydrophobic and ionic four-helical interfaces, which based on mutagenesis experiments, are critical for tetramerization. Strikingly, N-terminal BASS helices bend as they emerge from the central bundle, swapping partner helices, to form dimeric parallel coiled-coils at both ends, which are offset by 90°. We propose that BASS is a mechanically stable, plectonemically-coiled junction, transmitting forces between Kinesin-5 motor dimers during microtubule sliding.DOI: http://dx.doi.org/10.7554/eLife.02217.001

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Section: Introductionmentioning

confidence: 99%

Structural basis for the assembly of the mitotic motor Kinesin-5 into bipolar tetramers

Nithianantham

Scholey

Al-Bassam

2014

eLife

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“…Microtubule-associated motor proteins have important functions in spindle assembly. They organize MTs arising from both spindle poles in a fusiform-structure as they promote embedding and clustering MT minus ends in the centrosome and allow MT plus-ends to have dynamic behavior, elongation/shortening, which promotes the capture of kinetochores during the early phase of mitosis [2]. The kinesin-13 family is critically involved in the process of spindle assembly.…”

Section: Introductionmentioning

confidence: 99%

Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis

et al. 2014

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Proper bi-orientation of chromosomes is critical for the accurate segregation of chromosomes in mitosis. A key regulator of this process is MCAK, the mitotic centromere-associated kinesin. During mitosis the activity and localization of MCAK are regulated by mitotic key kinases including Plk1 and Aurora B. We show here that S621 in the MCAK's C-terminal domain is the major phosphorylation site for Plk1. This phosphorylation regulates MCAK's stability and facilitates its recognition by the ubiquitin/proteasome dependent APC/CCdc20 pathway leading to its D-box dependent degradation in mitosis. While phosphorylation of S621 does not directly affect its microtubule depolymerising activity, loss of Plk1 phosphorylation on S621 indirectly enhances its depolymerization activity in vivo by stabilizing MCAK, leading to an increased level of protein. Interfering with phosphorylation at S621 causes spindle formation defects and chromosome misalignments. Therefore, this study suggests a new mechanism by which Plk1 regulates MCAK: by regulating its degradation and hence controlling its turnover in mitosis.

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“…Mitosis relies on a multitude of protein complexes, protein-protein interactions, and regulatory mechanisms (Walczak and Heald, 2008). To date, many proteins that associate with microtubules and function in mitotic spindle assembly have been identified and characterized (Loughlin et al, 2008; Manning and Compton, 2008a, b; Walczak and Heald, 2008). Non-motor proteins, for example, function in microtubule nucleation, crosslinking, and stability, and can influence the activities of motor proteins (Manning and Compton, 2008b).…”

Section: Introductionmentioning

confidence: 99%

The STARD9/Kif16a Kinesin Associates with Mitotic Microtubules and Regulates Spindle Pole Assembly

Torres

Summers

Peterson³

et al. 2011

Cell

112

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SUMMARY During cell division cells form the microtubule-based mitotic spindle, a highly specialized and dynamic structure that mediates proper chromosome transmission to daughter cells. Cancer cells can show perturbed mitotic spindles and an approach in cancer treatment has been to trigger cell killing by targeting microtubule dynamics or spindle assembly. To identify and characterize proteins necessary for spindle assembly, and potential antimitotic targets, we performed a proteomic and genetic analysis of 592 mitotic microtubule co-purifying proteins (MMCPs). Screening for regulators that affect both mitosis and apoptosis, we report the identification and characterization of STARD9, a kinesin-3 family member, which localizes to centrosomes and stabilizes the pericentriolar material (PCM). STARD9-depleted cells have fragmented PCM, form multipolar spindles, activate the spindle assembly checkpoint (SAC), arrest in mitosis, and undergo apoptosis. Interestingly, STARD9-depletion synergizes with the chemotherapeutic agent taxol to increase mitotic death, demonstrating that STARD9 is a mitotic kinesin and a potential anti-mitotic target.

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SnapShot: Motor Proteins in Spindle Assembly

Cited by 13 publications

References 10 publications

Structural basis for the assembly of the mitotic motor Kinesin-5 into bipolar tetramers

Structural basis for the assembly of the mitotic motor Kinesin-5 into bipolar tetramers

Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis

The STARD9/Kif16a Kinesin Associates with Mitotic Microtubules and Regulates Spindle Pole Assembly

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