(mentions CMT) The downside of microtubule stability

[Guest guest]

The downside of microtubule stability

Study shows stalled microtubules might be responsible for some cases of the

neurological disorder Charcot-Marie-Tooth disease

http://www.eurekalert.org/pub_releases/2009-06/rup-tdo060309.php

Stalled microtubules might be responsible for some cases of the neurological

disorder Charcot-Marie-Tooth (CMT) disease, Tanabe and Takei report in the June

15, 2009 issue of the Journal of Cell Biology (www.jcb.org). 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 microtuble dynamics during the cell cycle.