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http://purl.uniprot.org/citations/34309047http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34309047http://www.w3.org/2000/01/rdf-schema#comment"Tubulin polyglutamylation is a post-translational modification of the microtubule cytoskeleton, which is generated by a variety of enzymes with different specificities. The "tubulin code" hypothesis predicts that modifications generated by specific enzymes selectively control microtubule functions. Our recent finding that excessive accumulation of polyglutamylation in neurons causes their degeneration and perturbs axonal transport provides an opportunity for testing this hypothesis. By developing novel mouse models and a new glutamylation-specific antibody, we demonstrate here that the glutamylases TTLL1 and TTLL7 generate unique and distinct glutamylation patterns on neuronal microtubules. We find that under physiological conditions, TTLL1 polyglutamylates α-tubulin, while TTLL7 modifies β-tubulin. TTLL1, but not TTLL7, catalyses the excessive hyperglutamylation found in mice lacking the deglutamylase CCP1. Consequently, deletion of TTLL1, but not of TTLL7, prevents degeneration of Purkinje cells and of myelinated axons in peripheral nerves in these mice. Moreover, loss of TTLL1 leads to increased mitochondria motility in neurons, while loss of TTLL7 has no such effect. By revealing how specific patterns of tubulin glutamylation, generated by distinct enzymes, translate into specific physiological and pathological readouts, we demonstrate the relevance of the tubulin code for homeostasis."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.org/dc/terms/identifier"doi:10.15252/embj.2021108498"xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/author"Klein D."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/author"Yuan X."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/author"Janke C."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/author"Magiera M.M."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/author"Martini R."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/author"Birling M.C."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/author"Bodakuntla S."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/author"Gadadhar S."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/author"Leboucher S."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/author"Genova M."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/name"EMBO J"xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/pages"e108498"xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/title"Distinct roles of alpha- and beta-tubulin polyglutamylation in controlling axonal transport and in neurodegeneration."xsd:string
http://purl.uniprot.org/citations/34309047http://purl.uniprot.org/core/volume"40"xsd:string
http://purl.uniprot.org/citations/34309047http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/34309047
http://purl.uniprot.org/citations/34309047http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/34309047
http://purl.uniprot.org/uniprot/#_A0A0G2LB90-mappedCitation-34309047http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34309047
http://purl.uniprot.org/uniprot/#_E9Q6C6-mappedCitation-34309047http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34309047
http://purl.uniprot.org/uniprot/#_A0A0G2JFF6-mappedCitation-34309047http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34309047
http://purl.uniprot.org/uniprot/#_A0A286YDV2-mappedCitation-34309047http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34309047
http://purl.uniprot.org/uniprot/#_A0A286YDY7-mappedCitation-34309047http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34309047