Publications

• Writing and Reading the Tubulin Code.

  Yu I., Garnham C.P., Roll-Mecak A.

  Microtubules give rise to intracellular structures with diverse morphologies and dynamics that are crucial for cell division, motility, and differentiation. They are decorated with abundant and chemically diverse posttranslational modifications that modulate their stability and interactions with c ... >> More

  Microtubules give rise to intracellular structures with diverse morphologies and dynamics that are crucial for cell division, motility, and differentiation. They are decorated with abundant and chemically diverse posttranslational modifications that modulate their stability and interactions with cellular regulators. These modifications are important for the biogenesis and maintenance of complex microtubule arrays such as those found in spindles, cilia, neuronal processes, and platelets. Here we discuss the nature and subcellular distribution of these posttranslational marks whose patterns have been proposed to constitute a tubulin code that is interpreted by cellular effectors. We review the enzymes responsible for writing the tubulin code, explore their functional consequences, and identify outstanding challenges in deciphering the tubulin code. << Less

  J Biol Chem 290:17163-17172(2015) [PubMed] [EuropePMC]

  This publication is cited by 8 other entries.

• Tubulin polyglutamylase enzymes are members of the TTL domain protein family.

  Janke C., Rogowski K., Wloga D., Regnard C., Kajava A.V., Strub J.-M., Temurak N., van Dijk J., Boucher D., van Dorsselaer A., Suryavanshi S., Gaertig J., Edde B.

  Polyglutamylation of tubulin has been implicated in several functions of microtubules, but the identification of the responsible enzyme(s) has been challenging. We found that the neuronal tubulin polyglutamylase is a protein complex containing a tubulin tyrosine ligase-like (TTLL) protein, TTLL1. ... >> More

  Polyglutamylation of tubulin has been implicated in several functions of microtubules, but the identification of the responsible enzyme(s) has been challenging. We found that the neuronal tubulin polyglutamylase is a protein complex containing a tubulin tyrosine ligase-like (TTLL) protein, TTLL1. TTLL1 is a member of a large family of proteins with a TTL homology domain, whose members could catalyze ligations of diverse amino acids to tubulins or other substrates. In the model protist Tetrahymena thermophila, two conserved types of polyglutamylases were characterized that differ in substrate preference and subcellular localization. << Less

  Science 308:1758-1762(2005) [PubMed] [EuropePMC]

  This publication is cited by 8 other entries.

• Polyglutamylation is a post-translational modification with a broad range of substrates.

  van Dijk J., Miro J., Strub J.M., Lacroix B., van Dorsselaer A., Edde B., Janke C.

  Polyglutamylation is a post-translational modification that generates lateral acidic side chains on proteins by sequential addition of glutamate amino acids. This modification was first discovered on tubulins, and it is important for several microtubule functions. Besides tubulins, only the nucleo ... >> More

  Polyglutamylation is a post-translational modification that generates lateral acidic side chains on proteins by sequential addition of glutamate amino acids. This modification was first discovered on tubulins, and it is important for several microtubule functions. Besides tubulins, only the nucleosome assembly proteins NAP1 and NAP2 have been shown to be polyglutamylated. Here, using a proteomic approach, we identify a large number of putative substrates for polyglutamylation in HeLa cells. By analyzing a selection of these putative substrates, we show that several of them can serve as in vitro substrates for two of the recently discovered polyglutamylases, TTLL4 and TTLL5. We further show that TTLL4 is the main polyglutamylase enzyme present in HeLa cells and that new substrates of polyglutamylation are indeed modified by TTLL4 in a cellular context. No clear consensus polyglutamylation site could be defined from the primary sequence of the here-identified new substrates of polyglutamylation. However, we demonstrate that glutamate-rich stretches are important for a protein to become polyglutamylated. Most of the newly identified substrates of polyglutamylation are nucleocytoplasmic shuttling proteins, including many chromatin-binding proteins. Our work reveals that polyglutamylation is a much more widespread post-translational modification than initially thought and thus that it might be a regulator of many cellular processes. << Less

  J Biol Chem 283:3915-3922(2008) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• A targeted multienzyme mechanism for selective microtubule polyglutamylation.

  van Dijk J., Rogowski K., Miro J., Lacroix B., Edde B., Janke C.

  Polyglutamylases are enzymes that form polyglutamate side chains of variable lengths on proteins. Polyglutamylation of tubulin is believed to regulate interactions of microtubules (MTs) with MT-associated proteins and molecular motors. Subpopulations of MTs are differentially polyglutamylated, yet ... >> More

  Polyglutamylases are enzymes that form polyglutamate side chains of variable lengths on proteins. Polyglutamylation of tubulin is believed to regulate interactions of microtubules (MTs) with MT-associated proteins and molecular motors. Subpopulations of MTs are differentially polyglutamylated, yet only one modifying enzyme has been discovered in mammals. In an attempt to better understand the heterogeneous appearance of tubulin polyglutamylation, we searched for additional enzymes and report here the identification of six mammalian polyglutamylases. Each of them has a characteristic mode of catalysis and generates distinct patterns of modification on MTs, which can be further diversified by cooperation of multiple enzymes. Polyglutamylases are restricted to confined tissues and subtypes of MTs by differential expression and localization. In conclusion, we propose a multienzyme mechanism of polyglutamylation that can explain how the diversity of polyglutamylation on selected types of MTs is controlled at the molecular level. << Less

  Mol. Cell 26:437-448(2007) [PubMed] [EuropePMC]

  This publication is cited by 8 other entries.

• Structure of the polyglutamyl side chain posttranslationally added to alpha-tubulin.

  Redeker V., Le Caer J.P., Rossier J., Prome J.C.

  Polyglutamylation, a new posttranslational modification of tubulin identified originally on the acidic alpha variants by Eddé et al. (Eddé, B., Rossier, J., Le Caer, J. P., Desbruyeres, E., Gros, F., and Denoulet, P. (1990) Science 247, 83-85), consists of the successive addition of glutamyl units ... >> More

  Polyglutamylation, a new posttranslational modification of tubulin identified originally on the acidic alpha variants by Eddé et al. (Eddé, B., Rossier, J., Le Caer, J. P., Desbruyeres, E., Gros, F., and Denoulet, P. (1990) Science 247, 83-85), consists of the successive addition of glutamyl units to the Glu445. To characterize their linkage mode mouse tubulin was posttranslationally labeled with [3H]glutamate. After digestion of [3H]tubulin with thermolysin, up to eight radioactive peaks were separated on an anion exchange column (DEAE). Combined use of Edman degradation sequencing and mass spectrometry analysis of the first 6 one indicated that they all correspond to the same COOH-terminal sequence 440VEGEGEEEGEE450 bearing one to six glutamyl units on the Glu445. The first glutamyl residue is amide-linked to the gamma-carboxyl group of Glu445, but the additional residues can be linked to the gamma- or alpha-carboxyl groups of the preceding one. All possible linkages for the biglutamylated tubulin peptides (gamma 1 alpha 2, gamma 1 gamma 2) and triglutamylated (gamma 1 alpha 2 alpha 3, gamma 1 alpha 2 gamma 3, gamma 1 alpha 2 gamma 2, gamma 1 gamma 2 alpha 3, gamma 1 gamma 2 gamma 3) were synthesized. These different peptides were successfully separated on a C18 5-micron reverse phase column. We found that the bi- and triglutamylated tubulin peptides behave as the gamma 1 alpha 2 and gamma 1 alpha 2 alpha 3 synthetic peptides, respectively. These results indicate that the second and third glutamyl residues of the polyglutamyl side chain are amide-linked to the alpha-carboxyl group of the preceding unit. << Less

  J Biol Chem 266:23461-23466(1991) [PubMed] [EuropePMC]

  This publication is cited by 8 other entries.