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The downside of microtubule stability

In a cell lacking dynamin 2, the pre-Golgi vesicles (green spheres) remain dispersed.

Stalled microtubules might be responsible for some cases of the neurological disorder Charcot-Marie-Tooth (CMT) disease, Tanabe and Takei report. A mutant protein makes the microtubules too stable to perform their jobs, the researchers find.

The mutations behind CMT disease slow nerve impulses, reduce their strength, or both. One of these mutations leads to production of faulty dynamin 2, a protein that is crucial for endocytosis but also latches onto microtubules. Tanabe and Takei investigated how defective dynamin 2 hampers cells.

Normal microtubules are continually extending and shrinking. But microtubules from cells that made the faulty version of dynamin 2 were abnormally stable, as measured by how many acetyl groups were attached to them. The researchers also found that blocking normal dynamin 2 with RNAi had the same effect as the mutation, confirming that one of dynamin 2's functions is to promote microtubule turnover.

Removing dynamin 2 shattered the Golgi complex, Tanabe and Takei discovered. Dynamic microtubules help construct the Golgi complex in two ways: they capture the vesicles that combine to form a mature Golgi complex; and they provide a track along which these vesicles can travel to their rendezvous point near the nucleus. By breaking up the Golgi apparatus and then watching the fragments reunite, the researchers found that dynamin 2 was essential for the capture step, not for transportation. Dynamin 2 also clings to microtubules of the mitotic spindle, and the team next wants to determine whether the protein regulates microtubule dynamics during the cell cycle.

References

Tanabe, K., and K. Takei. 2009. J. Cell Biol. doi:10.1083/jcb.200803153.[Abstract/Free Full Text]

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This Article Full Text (PDF, 565K) 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 Leslie, M. PubMed Articles by Leslie, M. Social Bookmarking                            What's this?