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Bringing stability to microtubules

MCAK (green) binds less efficiently to microtubules (red) when -tubulin is detyrosinated (right), increasing their stability.

The removal of a single tyrosine residue from the C terminus of -tubulin dramatically affects microtubules and their depolymerizing motors, say Peris et al.

-tubulin undergoes a cycle of tyrosine removal and readdition, catalyzed by a carboxypeptidase and tubulin tyrosine ligase (TTL). Microtubules containing detyrosinated -tubulin are more stable, and this modification is often used as a marker to distinguish different populations of microtubules within cells. But removing tyrosine was thought to be a consequence rather than a cause of microtubule stability.

Peris et al. examined the cytoskeletal dynamics of cells whose -tubulin is largely detyrosinated because they lack TTL. Microtubules disassembled more slowly in these cells, suggesting that detyrosination actually causes microtubule stability. Detyrosinated microtubules are poor substrates for depolymerizing motor proteins, the team discovered. Kinesin motors such as MCAK take longer to move along the filament and disassemble the tubulin subunits.

Overexpressing MCAK in cells lacking TTL restored normal microtubule dynamics, whereas removing MCAK from wild-type cells caused microtubules to stabilize as if they were detyrosinated. By showing that the absence of tyrosine reduces the activity of depolymerizing motors, the researchers have answered the conundrum of why stable microtubules are detyrosinated. Senior author Annie Andrieux now wants to solve another long-term mystery by identifying the tubulin caroboxypeptidase responsible for removing tyrosine in the first place.

References

Peris, L., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200902142.[Abstract/Free Full Text]

bshort{at}rockefeller.edu

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This Article Full Text (PDF, 509K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Short, B. PubMed Articles by Short, B. Social Bookmarking                            What's this?