A microtubule-associated protein from Xenopus eggs that specifically promotes assembly at the plus-end.

Gard, David L.; Kirschner, Marc W.

doi:10.1083/jcb.105.5.2203

Cited by 333 publications

(299 citation statements)

References 32 publications

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“…The founding member of this family, XMAP215, is required for rapid microtubule growth in Xenopus laevis egg extracts and accelerates elongation of the fastgrowing plus ends of microtubules by up to 8-fold in the presence of purified bovine brain tubulin (7). Tea1, the Aspergillus nidulans homolog of XMAP215, accelerates the growth of porcine brain microtubules to a similar extent as XMAP215 (8).…”

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confidence: 94%

Stu2, the Budding Yeast XMAP215/Dis1 Homolog, Promotes Assembly of Yeast Microtubules by Increasing Growth Rate and Decreasing Catastrophe Frequency

Podolski

Mahamdeh

Howard

2014

Journal of Biological Chemistry

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Background:The reported inhibition of microtubule growth by Stu2 is difficult to reconcile with its cellular phenotypes. Results: Using microscopy assays, we found that Stu2 increases the growth rate and decreases the catastrophe frequency of yeast microtubules. Conclusion: Stu2 promotes microtubule growth, with considerably higher activity on budding yeast microtubules. Significance: The biochemical properties of Stu2 reported here account for the mitotic phenotypes observed in cells.

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confidence: 94%

Stu2, the Budding Yeast XMAP215/Dis1 Homolog, Promotes Assembly of Yeast Microtubules by Increasing Growth Rate and Decreasing Catastrophe Frequency

Podolski

Mahamdeh

Howard

2014

Journal of Biological Chemistry

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“…DdCP224 from D. discoideum was detected at the centrosome and more weakly along microtubules throughout the entire cell cycle; furthermore, it binds to microtubules in vitro (11). XMAP215 from Xenopus promotes the formation of long microtubules by increasing the rate of microtubule polymerization, particularly at the plus end (4,45). Expression of truncated segments of XMAP215 in vivo (46) showed that the entire protein participates in microtubule binding.…”

Section: Effect Of Togp On Tubulin Polymerization; Effect Of Tubulin mentioning

confidence: 99%

“…2 This last group is composed of structural MAPs (MAP2, tau) that were first identified in brain tissue and of a group of XMAP215-related proteins whose generic member was first characterized in Xenopus eggs (4). TOGp (HUGO gene CKAP5), which is highly expressed in tumors and brain (5), is the human homolog of XMAP215.…”

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confidence: 99%

Kinetic Analysis of Tubulin Assembly in the Presence of the Microtubule-associated Protein TOGp

Bonfils

Bec

Lacroix

et al. 2007

Journal of Biological Chemistry

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The microtubule-associated protein TOGp, which belongs to a widely distributed protein family from yeasts to humans, is highly expressed in human tumors and brain tissue. From purified components we have determined the effect of TOGp on thermally induced tubulin association in vitro in the presence of 1 mM GTP and 3.4 M glycerol. Physicochemical parameters describing the mechanism of tubulin polymerization were deduced from the kinetic curves by application of the classical theoretical models of tubulin assembly. We have calculated from the polymerization time curves a range of parameters characteristic of nucleation, elongation, or steady state phase. In addition, the tubulin subunits turnover at microtubule ends was deduced from tubulin GTPase activity. For comparison, parallel experiments were conducted with colchicine and taxol, two drugs active on microtubules and with tau, a structural microtubule-associated protein from brain tissue. TOGp, which decreases the nucleus size and the tenth time of the reaction (the time required to produce 10% of the final amount of polymer), shortens the nucleation phase of microtubule assembly. In addition, TOGp favors microtubule formation by increasing the apparent first order rate constant of elongation. Moreover, TOGp increases the total amount of polymer by decreasing the tubulin critical concentration and by inhibiting depolymerization during the steady state of the reaction.Microtubules are highly dynamic structures that switch between growing and shrinking phases both in vivo and in vitro. These cytoskeleton polymers are necessary for many functions within the cell including intracellular transport, motility, morphogenesis, and cell division. The intrinsic dynamic instability of microtubules is further modified in the cell by numerous protein factors that favor alternatively elongation, shortening, or anchoring of these polymers. Because the mitotic spindle plays a crucial role in cell division, it has been used for decades as an important target in cancer chemotherapy. Many tubulin poisons have been identified, some of them, taxanes and vinca alkaloids, have demonstrated therapeutic value. However, all tubulin poisons are not of clinical utility. This has led to extensive efforts to explore other targets that could affect spindle integrity. A promising approach is to identify the protein regulators that modulate tubulin polymerization and to investigate their mechanism of action.The dynamic instability of microtubules is controlled in vivo by several classes of cellular factors including depolymerizing kinesins (MCAK/XKCM1) (1, 2), stathmins (3), and microtubule-associated proteins (MAPs).2 This last group is composed of structural MAPs (MAP2, tau) that were first identified in brain tissue and of a group of XMAP215-related proteins whose generic member was first characterized in Xenopus eggs (4). TOGp (HUGO gene CKAP5), which is highly expressed in tumors and brain (5), is the human homolog of XMAP215. TOGp promotes microtubule assembly both in solution and from n...

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“…It was identified as a factor increasing microtubule polymerization rates in Xenopus egg extracts (5). In vivo studies have shown that disruption of XMAP215 function leads to short interphase microtubules, reduced microtubule growth rate, and increased frequency of microtubule catastrophe and pause events (6)(7)(8)(9)(10)(11).…”

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confidence: 99%

The growth speed of microtubules with XMAP215-coated beads coupled to their ends is increased by tensile force

Trushko

Schäffer

Howard

2013

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

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The generation of pulling and pushing forces is one of the important functions of microtubules, which are dynamic and polarized structures. The ends of dynamic microtubules are able to form relatively stable links to cellular structures, so that when a microtubule grows it can exert a pushing force and when it shrinks it can exert a pulling force. Microtubule growth and shrinkage are tightly regulated by microtubule-associated proteins (MAPs) that bind to microtubule ends. Given their localization, MAPs may be exposed to compressive and tensile forces. The effect of such forces on MAP function, however, is poorly understood. Here we show that beads coated with the microtubule polymerizing protein XMAP215, the Xenopus homolog of Dis1 and chTOG, are able to link stably to the plus ends of microtubules, even when the ends are growing or shrinking; at growing ends, the beads increase the polymerization rate. Using optical tweezers, we found that tensile force further increased the microtubule polymerization rate. These results show that physical forces can regulate the activity of MAPs. Furthermore, our results show that XMAP215 can be used as a handle to sense and mechanically manipulate the dynamics of the microtubule tip.microtubule polymerase | microtubule dynamics | optical trap X MAP215 is a microtubule plus-end binding protein that alters microtubule dynamics (1-4) by promoting microtubule growth. It was identified as a factor increasing microtubule polymerization rates in Xenopus egg extracts (5). In vivo studies have shown that disruption of XMAP215 function leads to short interphase microtubules, reduced microtubule growth rate, and increased frequency of microtubule catastrophe and pause events (6-11). Depletion of XMAP215 also results in short, abnormally formed mitotic spindles and short astral microtubules (7,12,13). In vitro studies have demonstrated that XMAP215 binds preferentially to the microtubule plus end and follows the growth and shrinkage of the microtubule tip, catalyzing microtubule growth (14-16). In addition to localization at the microtubule plus end and centrosomes (17-19), proteins of the XMAP215/Dis1 family are found at the kinetochores (9, 20, 21), which are sites of high force during cell division. Microtubules themselves can exert pulling and pushing forces (22)(23)(24)(25)(26)(27)(28)(29)(30). Therefore, the localization of XMAP215 at microtubule ends suggests that XMAP215 can function under load. However, the effect of forces on XMAP215 activity has not been directly analyzed. In this study, we investigated the influence of forces-directed toward the microtubule plus and minus end-on XMAP215 activity in vitro. Microtubule growth and shrinkage were monitored with high spatial and temporal resolution by visualizing the position of XMAP215-coated polystyrene microspheres bound to the tips of dynamic microtubules. The microspheres, so-called "beads," served as handles to apply forces on XMAP215 molecules using optical tweezers. Results XMAP215-Coated Beads Remain Attached to Growing ...

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A microtubule-associated protein from Xenopus eggs that specifically promotes assembly at the plus-end.

Cited by 333 publications

References 32 publications

Stu2, the Budding Yeast XMAP215/Dis1 Homolog, Promotes Assembly of Yeast Microtubules by Increasing Growth Rate and Decreasing Catastrophe Frequency

Stu2, the Budding Yeast XMAP215/Dis1 Homolog, Promotes Assembly of Yeast Microtubules by Increasing Growth Rate and Decreasing Catastrophe Frequency

Kinetic Analysis of Tubulin Assembly in the Presence of the Microtubule-associated Protein TOGp

The growth speed of microtubules with XMAP215-coated beads coupled to their ends is increased by tensile force

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