ArticleThe Journal of cell biology2017
Mutation of the α-tubulin Tuba1a leads to straighter microtubules and perturbs neuronal migration.
Article in The Journal of cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 66 citations in OpenAlex.
- Towards a systems-level view of the microtubule cytoskeleton and its functions in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Structural dynamics of microtubules in glioma: impact on macrophage M2 polarization and tumor cell heterogeneity.Journal of translational medicine · 2026Article
- Microtubule-Targeting Agents: Advances in Tubulin Binding and Small Molecule Therapy for Gliomas and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Doublecortin restricts neuronal branching by regulating tubulin polyglutamylation.Nature communications · 2025Article
- Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies.Biomolecules · 2025Review
- Measurements of neurite extension and nucleokinesis in an iPSC-derived model system following microtubule perturbation.Molecular biology of the cell · 2025Article
- Spatiotemporal modeling reveals high-resolution invasion states in glioblastoma.Genome biology · 2024Article
- A circle of life: platelet and megakaryocyte cytoskeleton dynamics in health and disease.Open biology · 2024Review
- Connecting neurodevelopment to neurodegeneration: a spotlight on the role of kinesin superfamily protein 2A (KIF2A).Neural regeneration research · 2024Review
- Insights on the Role of α- and β-Tubulin Isotypes in Early Brain Development.Molecular neurobiology · 2023Review
- Microtubules composed of α4A undergo curved growth mainly mediated by its core structure.Journal of molecular cell biology · 2023Article
- Deciphering the Tubulin Language: Molecular Determinants and Readout Mechanisms of the Tubulin Code in Neurons.International journal of molecular sciences · 2023Review
- Deregulation of microtubule organization and RNA metabolism in Arx models for lissencephaly and developmental epileptic encephalopathy.Human molecular genetics · 2022Article
- Article
- Deciphering heterogeneous populations of migrating cells based on the computational assessment of their dynamic properties.Stem cell reports · 2022Article
- The molecular biology of tubulinopathies: Understanding the impact of variants on tubulin structure and microtubule regulation.Frontiers in cellular neuroscience · 2022Review
- The murine ortholog of Kaufman oculocerebrofacial syndrome protein Ube3b regulates synapse number by ubiquitinating Ppp3cc.Molecular psychiatry · 2021Article
- Bridging the Gap: The Importance of TUBA1A α-Tubulin in Forming Midline Commissures.Frontiers in cell and developmental biology · 2021Article
- The Multifaceted Roles of Primary Cilia in the Development of the Cerebral Cortex.Frontiers in cell and developmental biology · 2021Review
- Primary cilium-dependent cAMP/PKA signaling at the centrosome regulates neuronal migration.Science advances · 2020Article
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13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain development involves extensive migration of neurons. Microtubules (MTs) are key cellular effectors of neuronal displacement that are assembled from α/β-tubulin heterodimers. Mutation of the α-tubulin isotype TUBA1A is associated with cortical malformations in humans. In this study, we provide detailed in vivo and in vitro analyses of Tuba1a mutants. In mice carrying a Tuba1a missense mutation (S140G), neurons accumulate, and glial cells are dispersed along the rostral migratory stream in postnatal and adult brains. Live imaging of Tuba1a-mutant neurons revealed slowed migration and increased neuronal branching, which correlated with directionality alterations and perturbed nucleus-centrosome (N-C) coupling. Tuba1a mutation led to increased straightness of newly polymerized MTs, and structural modeling data suggest a conformational change in the α/β-tubulin heterodimer. We show that Tuba8, another α-tubulin isotype previously associated with cortical malformations, has altered function compared with Tuba1a. Our work shows that Tuba1a plays an essential, noncompensated role in neuronal saltatory migration in vivo and highlights the importance of MT flexibility in N-C coupling and neuronal-branching regulation during neuronal migration.
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