title: Evidence for new C-terminally truncated variants of α- and β-tubulins.
abstract: Cellular α-tubulin can bear various carboxy-terminal sequences: full-length tubulin arising from gene neosynthesis is tyrosinated, and two truncated variants, corresponding to detyrosinated and Δ2 α‑tubulin, result from the sequential cleavage of one or two C-terminal residues, respectively. Here, by using a novel antibody named 3EG that is highly specific to the -EEEG C-terminal sequence, we demonstrate the occurrence in neuronal tissues of a new αΔ3‑tubulin variant corresponding to α1A/B‑tubulin deleted of its last three residues (EEY). αΔ3‑tubulin has a specific distribution pattern: its quantity in the brain is similar to that of αΔ2-tubulin around birth but is much lower in adult tissue. This truncated α1A/B-tubulin variant can be generated from αΔ2-tubulin by the deglutamylases CCP1, CCP4, CCP5, and CCP6 but not by CCP2 and CCP3. Moreover, using 3EG antibody, we identify a C‑terminally truncated β-tubulin form with the same -EEEG C-terminal sequence. Using mass spectrometry, we demonstrate that β2A/B-tubulin is modified by truncation of the four C-terminal residues (EDEA). We show that this newly identified βΔ4-tubulin is ubiquitously present in cells and tissues and that its level is constant throughout the cell cycle. These new C-terminally truncated α- and β-tubulin variants, both ending with -EEEG sequence, are expected to regulate microtubule physiology. Of interest, the αΔ3-tubulin seems to be related to dynamic microtubules, resembling tyrosinated-tubulin rather than the other truncated variants, and may have critical function(s) in neuronal development.
authors.affiliation: Université Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France Inserm, U1216, F-38000 Grenoble, France.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Aillaud
authors.affiliation: Université Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France Inserm, U1216, F-38000 Grenoble, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bosc
authors.affiliation: Université Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France Inserm, U1216, F-38000 Grenoble, France.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Saoudi
authors.affiliation: Université Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France Inserm, U1216, F-38000 Grenoble, France CEA, BIG-GPC, F-38000 Grenoble, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Denarier
authors.affiliation: Université Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France Inserm, U1216, F-38000 Grenoble, France.
authors.forename: Leticia
authors.initials: L
authors.lastname: Peris
authors.affiliation: Service d'Identification et de Caractérisation des Protéines par Spectrométrie de masse, CNRS, 91198 Gif-sur-Yvette, France.
authors.forename: Laila
authors.initials: L
authors.lastname: Sago
authors.affiliation: Centre de Recherche de Biochimie Macromoléculaire, CNRS, 34293 Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Taulet
authors.affiliation: Université Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France Inserm, U1216, F-38000 Grenoble, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Cieren
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona), Spain Institut Curie, 91405 Orsay, France Paris Sciences et Lettres Research University, 75005 Paris, France Centre National de la Recherche Scientifique, UMR3348, 91405 Orsay, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Tort
authors.affiliation: Institut Curie, 91405 Orsay, France Paris Sciences et Lettres Research University, 75005 Paris, France Centre National de la Recherche Scientifique, UMR3348, 91405 Orsay, France.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Magiera
authors.affiliation: Institut Curie, 91405 Orsay, France Paris Sciences et Lettres Research University, 75005 Paris, France Centre National de la Recherche Scientifique, UMR3348, 91405 Orsay, France.
authors.forename: Carsten
authors.initials: C
authors.lastname: Janke
authors.affiliation: Service d'Identification et de Caractérisation des Protéines par Spectrométrie de masse, CNRS, 91198 Gif-sur-Yvette, France Paris-Saclay Institute of Neuroscience, CNRS, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Redeker
authors.affiliation: Université Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France Inserm, U1216, F-38000 Grenoble, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Andrieux
authors.affiliation: Université Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France Inserm, U1216, F-38000 Grenoble, France moutinm@univ-grenoble-alpes.fr.
authors.forename: Marie-Jo
authors.initials: MJ
authors.lastname: Moutin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002268:Carboxypeptidases / Q000378:metabolism*; D002453:Cell Cycle; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014404:Tubulin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D014404:Tubulin; D014443:Tyrosine; D002268:Carboxypeptidases; D010453:Peptide Synthases; C112698:tubulin polyglutamylase