Trends in Cell Biology
ReviewXMAP215: a key component of the dynamic microtubule cytoskeleton
Section snippets
XMAP215 as a major factor promoting microtubule polymerization
Because minus ends are anchored at centrosomes, it is thought that most of the morphogenetic properties of microtubules occur in association with the plus ends 14., 16.. Minus-end dynamics are also involved in the dynamic properties of microtubule cytoskeletons 24., 25., but will not be discussed here. Detailed comparison of the dynamic parameters of microtubule plus ends in cells/Xenopus egg extracts and in vitro showed that, in physiological conditions, the catastrophe rate and the growth
XMAP215 antagonizes XKCM1-induced catastrophe in Xenopus egg extracts
These immunodepletion experiments suggested that the activity of XMAP215 opposed the activity of catastrophe factors in Xenopus egg extracts. So far, two catastrophe factors have been identified: one is Op18/stathmin and the other is XKCM1 10., 32., 33., 34.. Op18/stathmin is a small heat-stable protein abundant in many types of cancer cells [35] that was purified as a factor capable of destabilizing microtubules from calf thymus 32., 36.. On the other hand, XKCM1 is a Xenopus kinesin-related
Reconstitution of physiological microtubule dynamics
The effects of immunodepletions of XMAP215 and XKCM1 on microtubule dynamics in Xenopus extracts suggested that the coordinated action of these proteins might explain why microtubules in cells polymerize rapidly and exhibit high rates of catastrophe. This hypothesis was tested by combining these two factors with purified tubulin in vitro and assessing whether such a mixture could reconstitute essential features of physiological microtubule dynamic instability [43]. XKCM1 reduced the
The Dis1/XMAP215 family and microtubule dynamics
Is XMAP215 a special MAP required only for larger frog eggs or is it more generally required for microtubule dynamics? The cloning of XMAP215 revealed that it is a member of a conserved family of proteins [30] (Fig. 4) (see Ref. [47] for review). Members of this protein family were first reported to colocalize with microtubules in the fission yeast, Schizosaccharomyces pombe. Fission yeast Dis1 was originally isolated as a cold-temperature-sensitive mutant possessing a defect in sister
The mystery at minus ends
Both biochemical and genetic approaches have revealed that the Dis1/XMAP215 family has an essential function in microtubule dynamics at plus ends of microtubules. However, in spite of their essential function at plus ends, the predominant localization of these proteins in many organisms is at the minus ends 65., 66., 67., 68.. Domain analysis of XMAP215 suggested that its C-terminal domain is required for targeting to centrosomes [31]. The function of this protein at minus ends remains a
Concluding remarks
Recent studies have revealed that the Dis1/XMAP215 family MAPs are central to microtubule dynamics in vivo. They seem to be essential for producing the dynamic properties of microtubules under physiological conditions. They endow microtubules not only with the ability to promote fast polymerization but also with the flexibility to allow high catastrophe rates.
Over the years, many different proteins have been isolated in different systems that influence the dynamic properties of tubulin in vitro.
Acknowledgements
We thank J.W. Raff for stimulating discussion and D.N. Drechsel, H. Funabiki, J. Howard and E.D. Salmon for critical reading and helpful comments on the manuscript. K.K. was supported by an HFSP long-term fellowship and a research fellowship of Uehara Memorial Foundation.
References (73)
Sites of microtubule assembly and disassembly in the mitotic spindle
Cell
(1986)- et al.
Structural polarity and directional growth of microtubules of Chlamydomonas flagella
J. Mol. Biol.
(1974) - et al.
Beyond self assembly: from microtubules to morphogenesis
Cell
(1986) Real-time visualization of cell cycle-dependent changes in microtubule dynamics in cytoplasmic extracts
Cell
(1990)- et al.
Microtubule dynamics: treadmilling comes around again
Curr. Biol.
(1997) - et al.
Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules
Cell
(1996) XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly
Cell
(1996)Microtubule dynamics and tubulin interacting proteins
Curr. Opin. Cell Biol.
(2000)Stathmin: a relay phosphoprotein for multiple signal transduction?
Trends Biochem. Sci.
(1991)The oncoprotein 18/stathmin family of microtubule destabilizers
Curr. Opin. Cell Biol.
(2002)
Kin I kinesins are microtubule-destabilizing enzymes
Cell
XKCM1 acts on a single protofilament and requires the C terminus of tubulin
J. Mol. Biol.
The interaction of TOGp with microtubules and tubulin
J. Biol. Chem.
Two loci required for cytoplasmic organization in early embryos of Caenorhabditis elegans
Dev. Biol.
M phase-specific kinetochore proteins in fission yeast. Microtubule-associating Dis1 and Mtc1 display rapid separation and segregation during anaphase
Curr. Biol.
Molecular analysis of kinetochore-microtubule attachment in budding yeast
Cell
Spindle microtubule dynamics in sea urchin embryos. Analysis using fluorescence-labeled tubulin and measurements of fluorescence redistribution after laser photobleaching
J. Cell Biol.
Microtubules of the kinetochore fiber turn over in metaphase but not in anaphase
J. Cell Biol.
Polewards microtubule flux in the mitotic spindle: evidence from photoactivation of fluorescence
J. Cell Biol.
Tubulin dynamics in cultured mammalian cells
J. Cell Biol.
Microtubule formation in vitro in solutions containing low calcium concentrations
Science
Dynamic instability of microtubule growth
Nature
Visualization of the dynamic instability of individual microtubules by dark-field microscopy
Nature
Dynamic instability of individual microtubules analysed by video light microscopy: rate constants and transition frequencies
J. Cell Biol.
Microtubule polymerization dynamics
Annu. Rev. Cell Dev. Biol.
Microtubule assembly nucleated by isolated centrosomes
Nature
Control of microtubule dynamics and length by cyclin A- and cyclin B-dependent kinases in Xenopus egg extracts
J. Cell Biol.
Force generation by microtubule assembly/disassembly in mitosis and related movements
Mol. Biol. Cell
Morphogenetic properties of microtubules and mitotic spindle assembly
Cell
Real-time observations of microtubule dynamic instability in living cells
J. Cell Biol.
Kinetochores capture astral microtubules during chromosome attachment to the mitotic spindle: direct visualization in live newt lung cells
J. Cell Biol.
Formation in vitro of sperm pronuclei and mitotic chromosomes induced by amphibian ooplasmic components
Science
Cell cycle extracts
Methods Cell Biol.
How the transition frequencies of microtubule dynamic instability (nucleation, catastrophe, and rescue) regulate microtubule dynamics in interphase and mitosis: analysis using a Monte Carlo computer simulation
Mol. Biol. Cell
Cell cycle-dependent changes in microtubule dynamics in living cells expressing green fluorescent protein-alpha tubulin
Mol. Biol. Cell
Centrosomal control of microtubule dynamics
Proc. Natl. Acad. Sci. U. S. A.
Cited by (116)
Therapeutic strategies for tauopathies and drug repurposing as a potential approach
2022, Biochemical PharmacologyThe Orphan Kinesin PAKRP2 Achieves Processive Motility via a Noncanonical Stepping Mechanism
2019, Biophysical JournalStructural maintenance of chromosome (SMC) proteins link microtubule stability to genome integrity
2014, Journal of Biological ChemistryNdc80 internal loop interacts with Dis1/TOG to ensure proper kinetochore-spindle attachment in fission yeast
2011, Current BiologyCitation Excerpt :Having seen the striking instability of spindle microtubules in Ndc80-loop mutants, we wondered whether some microtubule-binding proteins might compensate for spindle defects when overproduced. Among six such proteins tested, only one protein, Dis1 (a homolog of TOG/XMAP215) [8, 9], partially rescued temperature sensitivity of the ndc80-21 mutant (Figure 3A; Figure S3A). As Dis1/TOG family members are not only microtubule-associated proteins but also microtubule polymerases [22], suppression by overproduced Dis1 appeared coherent.