Moreover, Black et al. (1984) documented that only about 6% of the tubulin is resistant to cold and calcium when these cultured neurons are homogenized. These observations

suggest that neurons RO4929097 manufacturer contain multiple classes of microtubule polymers that differ in stability. The relatively stable class is presumably rendered less dynamic by cofactors such as STOP and other microtubule-related proteins that function in this manner in other cell types (Slaughter and Black, 2003), whereas the most stable class is unique to neurons and rendered completely nondynamic by a modification of the tubulin itself. Brady’s group has now made significant progress toward solving the mystery of the modification that accounts for the unique properties of cold-stable tubulin. In their new article, they argue that the relevant modification is Selisistat manufacturer transglutaminase-catalyzed polyamination (Song et al., 2013).

This makes sense because polyamination is known to make proteins more basic, whereas most modifications make proteins more acidic or are neutral, and because polyamination is known to cause proteins to become stable, insoluble, and resistant to proteolysis. In addition, transglutaminase activity is known to increase as Florfenicol neurons mature. However, to date, there has been no evidence showing that brain tubulin is a substrate for this modification that may change microtubule stability. In the new article, Song et al. (2013) report eight independent lines of biochemical evidence favoring the view that the polyamination of tubulin by transglutaminase

contributes to the stabilization of microtubules in neurons. This is fascinating in that the more commonly studied tubulin modifications (acetylation and detyrosination) do not confer stability to microtubules but, rather, accumulate on microtubules that are more stable (Janke and Bulinski, 2011). Thus, polyamination by transglutaminase would be the first identified modification that not only directly confers stability to microtubules but also makes them unusually stable in comparison to other stability classes of microtubules. Song et al. (2013) present a model in which they posit that the polyamination step can occur on free tubulin, after which modified and unmodified tubulins intermingle during microtubule assembly. Additional modifications may occur on polymerized tubulin. This raises several questions.