The nucleoporin MEL-28 promotes RanGTP-dependent ?-tubulin recruitment and microtubule nucleation in mitotic spindle formation.

The GTP-bound form of the Ran GTPase (RanGTP), produced around chromosomes, drives nuclear envelope and nuclear pore complex (NPC) re-assembly after mitosis. The nucleoporin MEL-28/ELYS binds chromatin in a RanGTP-regulated manner and acts to seed NPC assembly. Here we show that, upon mitotic NPC disassembly, MEL-28 dissociates from chromatin and ...
re-localizes to spindle microtubules and kinetochores. MEL-28 directly binds microtubules in a RanGTP-regulated way via its C-terminal chromatin-binding domain. Using Xenopus egg extracts, we demonstrate that MEL-28 is essential for RanGTP-dependent microtubule nucleation and spindle assembly, independent of its function in NPC assembly. Specifically, MEL-28 interacts with the ?-tubulin ring complex and recruits it to microtubule nucleation sites. Our data identify MEL-28 as a RanGTP target that functions throughout the cell cycle. Its cell cycle-dependent binding to chromatin or microtubules discriminates MEL-28 functions in interphase and mitosis, and ensures that spindle assembly occurs only after NPC breakdown.
Mesh Terms:
Animals, Chromatin, DNA-Binding Proteins, HeLa Cells, Humans, Microtubule-Associated Proteins, Mitosis, Nuclear Pore, Spindle Apparatus, Transcription Factors, Tubulin, Xenopus, Xenopus Proteins, ran GTP-Binding Protein
Nat Commun
Date: Feb. 11, 2014
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