The dynein light chain (white) is normally recruited to NPCs (left), but recruitment is inefficient when Nup159 can’t be ubiquitylated (right).

The dynein light chain (white) is normally recruited to NPCs (left), but recruitment is inefficient when Nup159 can’t be ubiquitylated (right).

Hayakawa et al. reveal that many components of the yeast nuclear pore complex (NPC) are ubiquitylated and describe how this modification helps segregate the nucleus during mitosis.

NPCs and their constituent nucleoporin proteins control several cellular processes, including molecular transport between the nucleus and cytoplasm. These functions can be regulated by phosphorylation, but the effects of other posttranslational modifications, such as ubiquitylation, are less well understood. Hayakawa et al. systematically analyzed all 30 nucleoporins in the budding yeast S. cerevisiae and found that half of them were either mono- or polyubiquitylated.

The researchers focused on Nup159, a nucleoporin involved in mRNA export that is monoubiquitylated on a specific lysine residue by the SCF E3 ubiquitin ligase. Blocking this ubiquitylation didn't affect Nup159’s localization or mRNA transport, but it did reduce the nucleoporin's ability to recruit the dynein motor light chain to the nuclear envelope. In yeast, dynein attaches to NPCs and helps to orient the mitotic spindle and move the nucleus to the bud neck at the beginning of mitosis. Spindles were often misaligned and nuclear migration delayed in cells unable to ubiquitylate Nup159 and recruit dynein to NPCs. These defects became much more severe in cells that also lacked an alternative spindle orientation pathway involving the APC protein Kar9.

Senior author Catherine Dargemont now wants to investigate how ubiquitylation regulates the functions of the many other nucleoporins that undergo this posttranslational modification.

References

References
Hayakawa
A.
et al
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2012
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J. Cell Biol.
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