The molecular function of Ase1p

Schuyler, Scott C.; Liu, Jenny Y.; Pellman, David

doi:10.1083/jcb.200210021

Cited by 184 publications

(81 citation statements)

References 72 publications

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“…Note that in all cases (either with active motors or with passive angular diffusion), it was assumed that once a microtubule plus-end was within close proximity of the spindle axis (i.e. so that the spindle microtubule was nearly parallel to the spindle axis), other crosslinking proteins would “capture” the microtubule, and would thus hold the microtubule in place along the spindle axis for the remainder of the simulation (Schuyler et al, 2003). …”

Section: Resultsmentioning

confidence: 99%

“…Previous reports assign passive crosslinking proteins such as Ase1 (PRC1 in humans) an important role in the bundling of midzone microtubules during anaphase (Braun et al, 2011; Janson et al, 2007; Kapitein et al, 2005; Kotwaliwale et al, 2007; Loiodice et al, 2005; Schuyler et al, 2003). Similar to our simulation assumptions, we expect that crosslinking proteins other than Kinesin-14 may be required to maintain proper bundling within the midzone once interpolar microtubules are pivoted into alignment with the central spindle axis.…”

Section: Discussionmentioning

confidence: 99%

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Minus-End-Directed Kinesin-14 Motors Align Antiparallel Microtubules to Control Metaphase Spindle Length

et al. 2014

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Summary During cell division, a microtubule-based mitotic spindle mediates the faithful segregation of duplicated chromosomes into daughter cells. Proper length control of the metaphase mitotic spindle is critical to this process, and is thought to be achieved through a mechanism in which spindle pole separation forces from plus-end directed motors are balanced by forces from minus-end directed motors that pull spindle poles together. However, in contrast to this model, metaphase mitotic spindles with inactive Kinesin-14 minusend directed motors often have shorter spindle lengths, along with poorly aligned spindle microtubules. A mechanistic explanation for this paradox is unknown. Using computational modeling, in vitro reconstitution, live-cell fluorescence microscopy, and electron microscopy, we now find that the budding yeast Kinesin-14 molecular motor Kar3-Cik1 can efficiently align spindle microtubules along the spindle axis. This then allows plus-end directed Kinesin-5 motors to efficiently exert the outward microtubule sliding forces needed for proper spindle bipolarity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Minus-End-Directed Kinesin-14 Motors Align Antiparallel Microtubules to Control Metaphase Spindle Length

et al. 2014

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“…In this paper we examine MT organization at this larger scale and reveal a new role for MT crosslinkers of the MAP65/Ase1/PRC1 family [9–12]. In the absence of Ase1A in D. discoideum , MT arrays no longer maintain spatial separation in a multinucleated environment.…”

Section: Introductionmentioning

confidence: 99%

Organization of microtubule assemblies in Dictyostelium syncytia depends on the microtubule crosslinker, Ase1

Tikhonenko¹,

Irizarry²,

Khodjakov³

et al. 2015

Cell. Mol. Life Sci.

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It has long been known that the interphase microtubule (MT) array is a key cellular scaffold that provides structural support and directs organelle trafficking in eukaryotic cells. Although in animal cells, a combination of centrosome nucleating properties and polymer dynamics at the distal microtubule ends is generally sufficient to establish a radial, polar array of MTs, little is known about how effector proteins (motors and crosslinkers) are coordinated to produce the diversity of interphase MT array morphologies found in nature. This diversity is particularly important in multinucleated environments where multiple MT arrays must coexist and function. We initiate here a study to address the higher ordered coordination of multiple, independent MT arrays in a common cytoplasm. Deletion of a MT crosslinker of the MAP65/Ase1/PRC1 family disrupts the spatial integrity of multiple arrays in Dictyostelium discoideum, reducing the distance between centrosomes and increasing the intermingling of MTs with opposite polarity. This result, coupled with previous dynein disruptions suggest a robust mechanism by which interphase MT arrays can utilize motors and crosslinkers to sense their position and minimize overlap in a common cytoplasm.

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“…Cdk phosphorylation of PRC1 appears to be important for suppressing PRC1 MT-bundling activity in early mitosis, because a Cdk-nonphosphorylatable mutant of PRC1 causes extensive bundling of the metaphase spindle (9). Perturbing the function of PRC1 or PRC1-related orthologs in various species (Ase1p in yeast, SPD-1 in Caenorhabditis elegans, AtMAP65 in Arabidopsis, and Feo in Drosophila) inhibits the formation of midzone interdigitating MT bundles, resulting in two disarrayed half spindles (9)(10)(11)(12)(13)(14)(15). The centralspindlin complex, chromosomal passenger proteins, and other midzone-associated proteins mislocalize in PRC1-depleted anaphase cells (refs.…”

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confidence: 99%

Spatiotemporal control of spindle midzone formation by PRC1 in human cells

Zhu

Lau

Schwarzenbacher

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

149

165

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We have examined the role of PRC1, a midzone-associated, microtubule bundling, Cdk substrate protein, in regulating the spatiotemporal formation of the midzone in HeLa cells. Cdk-mediated phosphorylation of PRC1 in early mitosis holds PRC1 in an inactive monomeric state. During the metaphase-to-anaphase transition, PRC1 is dephosphorylated, promoting PRC1 oligomerization. Using time-lapse video microscopy, RNA interference, 3D immunofluorescence reconstruction imaging, and rescue experiments, we demonstrate that the dephosphorylated form of PRC1 is essential for bundling antiparallel, nonkinetochore, interdigitating microtubules to establish the midzone that is necessary for cytokinesis. Our results thus indicate that PRC1 is an essential factor in controlling the spatiotemporal formation of the midzone in human cells.Cdk phosphorylation ͉ mitosis͞cytokinesis ͉ microtubule-associated proteins ͉ microtubule bundling D uring the metaphase-to-anaphase transition, a conspicuous network of antiparallel nonkinetochore interdigitating microtubules (MTs) assembles between separating chromosomes. This unique structure is referred to as the spindle midzone. The midzone is believed to be required for the maintenance of overall spindle architecture, spindle elongation, and cleavage furrow positioning (1, 2). Previous studies indicated that the midzone-associated centralspindlin complex might play a crucial role in regulating midzone formation. The complex exists as a heterotetramer comprising the midzone-associated kinesin motor, MKLP1, and its binding protein, MgcRacGAP (a Rho-family GTPase activating protein) (3). The heterotetramer, but not the individual MKLP1 or MgcRacGAP proteins, has MT bundling activity (3). Cdk (Cdc2͞ cyclin B) phosphorylates MKLP1 and negatively regulates its motor and MT-bundling activities (4). Because inactivation of Cdk activity (through the destruction of cyclin B) is critical for the metaphaseto-anaphase transition, it was suggested that Cdk phosphorylation of MPLK1 controls the timing of midzone formation (4, 5). However, recent studies indicate that MKLP1 is not directly involved in the early stages of midzone formation in mammalian cells (6, 7). Immunofluorescence and time-lapse live cell imaging analyses revealed that inhibition of MKLP1 expression does not perturb the bundling of midzone interdigitating MTs. Instead, it inhibits midbody formation and the completion of cytokinesis. Thus, the centralspindlin complex is required for constricting the midzone and forming the midbody that is essential for completing cytokinesis in mammalian cells (7).PRC1 originally was identified as a Cdk substrate in an in vitro phosphorylation screen and was subsequently shown to be a midzone-associated protein required for cytokinesis (8). PRC1 forms oligomers in vivo and has 9). Cdk phosphorylation of PRC1 appears to be important for suppressing PRC1 MT-bundling activity in early mitosis, because a Cdk-nonphosphorylatable mutant of PRC1 causes extensive bundling of the metaphase spindle (9). Perturbing t...

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The molecular function of Ase1p

Cited by 184 publications

References 72 publications

Minus-End-Directed Kinesin-14 Motors Align Antiparallel Microtubules to Control Metaphase Spindle Length

Minus-End-Directed Kinesin-14 Motors Align Antiparallel Microtubules to Control Metaphase Spindle Length

Organization of microtubule assemblies in Dictyostelium syncytia depends on the microtubule crosslinker, Ase1

Spatiotemporal control of spindle midzone formation by PRC1 in human cells

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