ArticleHuman molecular genetics2019
Defective tubulin detyrosination causes structural brain abnormalities with cognitive deficiency in humans and mice.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 65 citations in OpenAlex.
- Post-Translational Modifications of Tubulin in Oocyte Maturation and Female Infertility.Cytoskeleton (Hoboken, N.J.) · 2026Review
- Condensation of MATCAP promotes CENP-E-dependent chromosome congression in mitosis.Nature communications · 2026Article
- Peptide-based covalent inhibitor of tubulin detyrosination promotes mesenchymal-to-epithelial transition in lung cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Effects of microtubule (de)tyrosination on the morphology and motility of Trypanosoma brucei and cross-talk with polyglutamylation.Biology open · 2025Article
- L-Dopa-modified microtubules lead to synapse instability in cultured neurons: possible implications in Parkinson's disease therapy.NPJ Parkinson's disease · 2025Article
- Mechanistic insights into TTLL11 polyglutamylase-mediated primary tubulin chain elongation.Science advances · 2025Article
- Review
- How does the tubulin code facilitate directed cell migration?Biochemical Society transactions · 2025Review
- Emerging roles for tubulin PTMs in neuronal function and neurodegenerative disease.Current opinion in neurobiology · 2025Review
- Tubulin tyrosination/detyrosination regulate the affinity and sorting of intraflagellar transport trains on axonemal microtubule doublets.Nature communications · 2025Article
- Altered tubulin detyrosination due to SVBP malfunction induces cytokinesis failure and senescence, underlying a complex hereditary spastic paraplegia.Aging cell · 2025Article
- Efficient axonal transport of endolysosomes relies on the balanced ratio of microtubule tyrosination and detyrosination.Journal of cell science · 2024Article
- Microtubule-binding protein MAP1B regulates interstitial axon branching of cortical neurons via the tubulin tyrosination cycle.The EMBO journal · 2024Article
- A family of carboxypeptidases catalyzing α- and β-tubulin tail processing and deglutamylation.Science advances · 2023Article
- Microtubule detyrosination drives symmetry breaking to polarize cells for directed cell migration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Microtubule acetylation dyshomeostasis in Parkinson's disease.Translational neurodegeneration · 2023Review
- Mechanistic Analysis of CCP1 in Generating ΔC2 α-Tubulin in Mammalian Cells and Photoreceptor Neurons.Biomolecules · 2023Article
- Role of tubulin post-translational modifications in peripheral neuropathy.Experimental neurology · 2023Review
- Tubulin tyrosination regulates synaptic function and is disrupted in Alzheimer's disease.Brain : a journal of neurology · 2022Article
- Article
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Authors and funding
27 authors at 11 institutions in 4 countries.
Funding
Abstract
Reversible detyrosination of tubulin, the building block of microtubules, is crucial for neuronal physiology. Enzymes responsible for detyrosination were recently identified as complexes of vasohibins (VASHs) one or two with small VASH-binding protein (SVBP). Here we report three consanguineous families, each containing multiple individuals with biallelic inactivation of SVBP caused by truncating variants (p.Q28* and p.K13Nfs*18). Affected individuals show brain abnormalities with microcephaly, intellectual disability and delayed gross motor and speech development. Immunoblot testing in cells with pathogenic SVBP variants demonstrated that the encoded proteins were unstable and non-functional, resulting in a complete loss of VASH detyrosination activity. Svbp knockout mice exhibit drastic accumulation of tyrosinated tubulin and a reduction of detyrosinated tubulin in brain tissue. Similar alterations in tubulin tyrosination levels were observed in cultured neurons and associated with defects in axonal differentiation and architecture. Morphological analysis of the Svbp knockout mouse brains by anatomical magnetic resonance imaging showed a broad impact of SVBP loss, with a 7% brain volume decrease, numerous structural defects and a 30% reduction of some white matter tracts. Svbp knockout mice display behavioural defects, including mild hyperactivity, lower anxiety and impaired social behaviour. They do not, however, show prominent memory defects. Thus, SVBP-deficient mice recapitulate several features observed in human patients. Altogether, our data demonstrate that deleterious variants in SVBP cause this neurodevelopmental pathology, by leading to a major change in brain tubulin tyrosination and alteration of microtubule dynamics and neuron physiology.
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