Trends in Cell Biology
Volume 12, Issue 6, 1 June 2002, Pages 267-273
Journal home page for Trends in Cell Biology

Review
XMAP215: a key component of the dynamic microtubule cytoskeleton

https://doi.org/10.1016/S0962-8924(02)02295-XGet rights and content

Abstract

Microtubules are essential for various cellular processes including cell division and intracellular organization. Their function depends on their ability to rearrange their distribution at different times and places. Microtubules are dynamic polymers and their behaviour is described as dynamic instability. Rearrangement of the microtubule cytoskeleton is made possible by proteins that modulate the parameters of dynamic instability. Studies using Xenopus egg extracts led to identification of a microtubule-associated protein called XMAP215 as a major regulator of physiological microtubule dynamics. XMAP215 belongs to an evolutionarily conserved protein family present in organisms ranging from yeast to mammals. Together with members of the Kin I family of kinesins, XMAP215 and its orthologues form an essential circuit for generating dynamic microtubules in vivo.

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.

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