Tubulin polyglutamylation stimulates spastin-mediated microtubule severing

Lacroix, Benjamin; Dijk, Juliette van; Gold, Nicholas D.; Guizetti, Julien; Aldrian, Gudrun; Rogowski, Krzysztof; Gerlich, Daniel W.; Janke, Carsten

doi:10.1083/jcb.201001024

Cited by 257 publications

(293 citation statements)

References 39 publications

Supporting

Mentioning

279

Contrasting

Order By: Relevance

“…2). The model is supported by the following data: (1) microtubules treated with subtilisin, a protease that cleaves the unstructured Cterminal tails of tubulin, cannot be severed (McNally and Vale, 1993;Roll-Mecak and Vale, 2005;White et al, 2007); (2) interestingly, the C-terminal tail is where most of the posttranslational modifications of tubulin occur (Verhey and Gaertig, 2007), and certain modifications, such as polyglutamylation, enhance the activity of severing (Lacroix et al, 2010); (3) mutations in the pore-loop region restrict and inhibit severing (Roll-Mecak and Vale, 2008;White et al, 2007) and these same pore mutants are unable to sever microtubules in cells, but are still able to bind and bundle microtubules (White et al, 2007); and (4) antibodies against the C-terminal tails of microtubules block severing activity (Roll-Mecak and Vale, 2008).…”

Section: Introductionmentioning

confidence: 56%

See 1 more Smart Citation

Microtubule-severing enzymes at the cutting edge

Sharp

Ross

2012

Journal of Cell Science

194

212

View full text Add to dashboard Cite

Summary ATP-dependent severing of microtubules was first reported in Xenopus laevis egg extracts in 1991. Two years later this observation led to the purification of the first known microtubule-severing enzyme, katanin. Katanin homologs have now been identified throughout the animal kingdom and in plants. Moreover, members of two closely related enzyme subfamilies, spastin and fidgetin, have been found to sever microtubules and might act alongside katanins in some contexts (Roll-Mecak and McNally, 2010;Yu et al., 2008;Zhang et al., 2007). Over the past few years, it has become clear that microtubule-severing enzymes contribute to a wide range of cellular activities including mitosis and meiosis, morphogenesis, cilia biogenesis and disassembly, and migration. Thus, this group of enzymes is revealing itself to be among the most important of the microtubule regulators. This Commentary focuses on our growing understanding of how microtubule-severing enzymes contribute to the organization and dynamics of diverse microtubule arrays, as well as the structural and biophysical characteristics that afford them the unique capacity to catalyze the removal of tubulin from the interior microtubule lattice. Our goal is to provide a broader perspective, focusing on a limited number of particularly informative, representative and/or timely findings.

show abstract

Section: Introductionmentioning

confidence: 56%

“…2). Numerous cellular studies have pointed to post-translational modification of the C-terminal tails of tubulin being the greatest indicators of severing activity (Lacroix et al, 2010;Sharma et al, 2007;Sudo and Baas, 2010) (Fig. 2).…”

Section: Introductionmentioning

confidence: 99%

Microtubule-severing enzymes at the cutting edge

Sharp

Ross

2012

Journal of Cell Science

194

212

View full text Add to dashboard Cite

show abstract

“…It is perhaps surprising that Atat1 knockout mice displayed only minor differences in neurological behaviour. a-tubulin acetylation has been suggested to influence kinesin-mediated transport 10 , and increase sensitivity of microtubules to severing in neuronal axons 43 , although these effects may be more dependent upon other tubulin modifications such as tyrosination 44,45 and polyglutamylation 46 . Migration and maturation of cortical neurons during development have also been reported to be dependent upon tubulin acetylation 14,47 , and depletion of mec17 in zebrafish leads to substantial neurological deficits 17 .…”

Section: Discussionmentioning

confidence: 99%

αTAT1 is the major α-tubulin acetyltransferase in mice

et al. 2013

View full text Add to dashboard Cite

Post-translational modification of tubulin serves as a powerful means for rapidly adjusting the functional diversity of microtubules. Acetylation of the e-amino group of K40 in a-tubulin is one such modification that is highly conserved in ciliated organisms. Recently, aTAT1, a Gcn5-related N-acetyltransferase, was identified as an a-tubulin acetyltransferase in Tetrahymena and C. elegans. Here we generate mice with a targeted deletion of Atat1 to determine its function in mammals. Remarkably, we observe a loss of detectable K40 a-tubulin acetylation in these mice across multiple tissues and in cellular structures such as cilia and axons where acetylation is normally enriched. Mice are viable and develop normally, however, the absence of Atat1 impacts upon sperm motility and male mouse fertility, and increases microtubule stability. Thus, aTAT1 has a conserved function as the major a-tubulin acetyltransferase in ciliated organisms and has an important role in regulating subcellular specialization of subsets of microtubules.

show abstract

“…In C. elegans, substitution of a glutamic acid residue in the CTT of -tubulin that is likely to serve in glutamylation rescues the embryonic lethality caused by overproduction of katanin (Lu et al, 2004). Overexpression of the TTLL11 E-ligase in HeLa cells causes fragmentation of microtubules that can be rescued by knockdown of spastin using small interfering RNA (siRNA); moreover, hyperglutamylated microtubules have increased sensitivity to spastin-mediated severing in vitro (Lacroix et al, 2010). Spastin (and probably katanin) are predicted to function as a ring complex of six subunits, with a centrally located pore that incorporates the tubulin CTT (RollMecak and Vale, 2008).…”

Section: Tubulin Ptms Affect the Organization And Dynamics Of Microtumentioning

confidence: 99%

Post-translational modifications of microtubules

Włoga

Gaertig

2010

Journal of Cell Science

230

137

View full text Add to dashboard Cite

There was an error published in J. Cell Sci. 123, 3447-3455.An incorrect version of Fig. 2 was published. The correct version, showing the severing of microtubules, is given below, together w its legend. We apologise for this mistake. CLIP-170Katanin, spastin There were errors published in J. Cell Sci. 123, 3447-3455.In Fig. 1, the arrows showing enzymatic reactions for MEC-17, HDAC6 and SIRT2 were pointing in the wrong direction. In addition, the C-terminal amino acid on the tail of -tubulin is Y (and not T). The correct figure is shown below.After publication of this Commentary, Shida and colleagues reported independent identification of MEC-17 homologs in diverse organisms as -tubulin acetyltransferases (Shida et al., 2010). Contrary to what we stated in our article and in the referenced paper (Akella et al., 2010), the newest version of the assembled genome of Chlamydomonas reinhardtii contains a sequence encoding an apparent homolog of the MEC-17 -tubulin acetyltransferase (locus ID Cre07.g345150).

show abstract

Tubulin polyglutamylation stimulates spastin-mediated microtubule severing

Abstract: Microtubules with long polyglutamylated C-terminal tails are more prone to severing by spastin, establishing the importance of tubulin posttranslational modifications.

Cited by 257 publications

References 39 publications

Microtubule-severing enzymes at the cutting edge

Microtubule-severing enzymes at the cutting edge

αTAT1 is the major α-tubulin acetyltransferase in mice

Post-translational modifications of microtubules

Contact Info

Product

Resources

About