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The Nup107-160 complex and γ-TuRC regulate microtubule polymerization at kinetochores


The metazoan nuclear pore complex (NPC) disassembles during mitosis, and many of its constituents distribute onto spindles and kinetochores, including the Nup107-160 sub-complex1,2. We have found that Nup107-160 interacts with the γ-tubulin ring complex (γ-TuRC), an essential and conserved microtubule nucleator3,4, and recruits γ-TuRC to unattached kinetochores. The unattached kinetochores nucleate microtubules in a manner that is regulated by Ran GTPase5; such microtubules contribute to the formation of kinetochore fibres (k-fibres)6, microtubule bundles connecting kinetochores to spindle poles. Our data indicate that Nup107-160 and γ-TuRC act cooperatively to promote spindle assembly through microtubule nucleation at kinetochores: HeLa cells lacking Nup107-160 or γ-TuRC were profoundly deficient in kinetochore-associated microtubule nucleation. Moreover, co-precipitated Nup107-160– γ-TuRC complexes nucleated microtubule formation in assays using purified tubulin. Although Ran did not regulate microtubule nucleation by γ-TuRC alone, Nup107-160–γ-TuRC complexes required Ran–GTP for microtubule nucleation. Collectively, our observations show that Nup107-160 promotes spindle assembly through Ran–GTP-regulated nucleation of microtubules by γ-TuRC at kinetochores, and reveal a relationship between nucleoporins and the microtubule cytoskeleton.

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Figure 1: Nup107-160 binds γ-TuRC.
Figure 2: γ-TuRC is recruited to kinetochores by Nup107-160.
Figure 3: Nup107-160 is critical for microtubule nucleation at kinetochores in HeLa cells.
Figure 4: Ran–GTP regulates microtubule nucleation by xNup107-160/γ-TuRC complexes.
Figure 5: Model for Nup107-160 and γ-TuRC regulation at kinetochores.


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R.K.M., A.A. and M.D. were supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural funds (Z01 HD008816 and Z01 HD008740). B.M.A.F. and P.C. were supported by National Institutes of Health R01 GM07159 and Texas HEB (Higher Education Board) 010019-0022-2006.

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All authors contributed to experimental design. R.K.M., A.A. and P.C. performed the experiments and analysed the data; M.D. wrote the manuscript.

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Correspondence to Mary Dasso.

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Mishra, R., Chakraborty, P., Arnaoutov, A. et al. The Nup107-160 complex and γ-TuRC regulate microtubule polymerization at kinetochores. Nat Cell Biol 12, 164–169 (2010).

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