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As an important neurotransmitter, glutamate acts in over 90% of excitatory synapses in the human brain. Its metabolic pathway is complicated, and the glutamate pool in neurons has not been fully elucidated. Tubulin polyglutamylation in the brain is mainly mediated by two tubulin tyrosine ligase-like (TTLL) proteins, TTLL1 and TTLL7, which have been indicated to be important for neuronal polarity. In this study, we constructed pure lines of and knockout mice. knockout mice showed several abnormal behaviors. Matrix-assisted laser desorption/ionization (MALDI) Imaging mass spectrometry (IMS) analyses of these brains showed increases in glutamate, suggesting that tubulin polyglutamylation by these TTLLs acts as a pool of glutamate in neurons and modulates some other amino acids related to glutamate.
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http://dx.doi.org/10.3390/biom13050784 | DOI Listing |
Sci Adv
August 2025
Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prumyslova 595, Vestec, Czech Republic.
Microtubules (MTs) undergo diverse posttranslational modifications that regulate their structural and functional properties. Among these, polyglutamylation-a dominant and conserved modification targeting unstructured tubulin C-terminal tails-plays a pivotal role in defining the tubulin code. Here, we describe a mechanism by which tubulin tyrosine ligase-like 11 (TTLL11) expands and diversifies the code.
View Article and Find Full Text PDFMicrotubules perform a variety of cellular functions including regulation of mitotic cell division, cilia formation, and neurite extension. Post-translational modifications controlled by the TTLL-family of enzymes confer a host of properties that affect microtubule dynamics and function. Specifically, polyglutamylation of tubulin C-terminal tails plays an important role in regulating microtubule dynamics and function within specific cellular contexts.
View Article and Find Full Text PDFJ Proteome Res
August 2025
Institut Pasteur, Université de Paris Cité, CNRS UAR 2024, Mass Spectrometry for Biology Unit, Paris 75015, France.
Tubulin polyglutamylation is a key feature of eukaryotic cilia and flagella that is essential for their function. The diversity of enzymes catalyzing polyglutamylation with different specificities inspired the hypothesis of the tubulin code. In the protist parasite , nine different glutamylase enzymes are potentially involved in tubulin glutamylation.
View Article and Find Full Text PDFNat Commun
June 2025
Institute of Neuronal Cell Biology, Technical University of Munich, Munich, Germany.
Developmental remodeling shapes neural circuits via activity-dependent pruning of synapses and axons. Regulation of the cytoskeleton is critical for this process, as microtubule loss via enzymatic severing is an early step of pruning across many circuits and species. However, how microtubule-severing enzymes, such as spastin, are activated in specific neuronal compartments remains unknown.
View Article and Find Full Text PDFProteins
June 2025
Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine, Кyiv, Ukraine.
Cell migration and motility, cell division, biogenesis and renewal of cell and tissue integrity, and the assembly and retention of cell or tissue architecture, to name but a few, represent increasingly vital processes at the cellular and whole-body levels. These biological processes are closely connected with the major structural transformations that cytoskeletal proteins undergo due to numerous post-translational modifications, including acetylation, tyrosynation, polyglutamylation, etc. We collected all the information on tubulin acetylation and data on related cellular manifestations.
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