ArticleHuman molecular genetics2010
Disease-associated mutations in TUBA1A result in a spectrum of defects in the tubulin folding and heterodimer assembly pathway.
Article in Human molecular genetics, 2010. 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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Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- Mutations in the β-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities.Cell reports · 2012Trial
- A unified mechanism for tubulin cofactors catalyzing α/β-tubulin biogenesis and degradation.Science advances · 2026Article
- The tubulin database: Linking mutations, modifications, ligands and local interactions.PloS one · 2023Article
- MAPping tubulin mutations.Frontiers in cell and developmental biology · 2023Review
- Case report: Structural brain abnormalities inFrontiers in pediatrics · 2023Article
- Functional Investigation of TUBB4A Variants Associated with Different Clinical Phenotypes.Molecular neurobiology · 2022Article
- Decreased tubulin-binding cofactor B was involved in the formation disorder of nascent astrocyte processes by regulating microtubule plus-end growth through binding with end-binding proteins 1 and 3 after chronic alcohol exposure.Frontiers in cellular neuroscience · 2022Article
- The molecular biology of tubulinopathies: Understanding the impact of variants on tubulin structure and microtubule regulation.Frontiers in cellular neuroscience · 2022Review
- Review
- Loss-of-Function Plays a Major Role in Early Neurogenesis of Tubulin α-1 A (TUBA1A) Mutation-Related Brain Malformations.Molecular neurobiology · 2021Article
- Kinetically Stabilizing Mutations in Beta Tubulins Create Isotype-Specific Brain Malformations.Frontiers in cell and developmental biology · 2021Article
- Bridging the Gap: The Importance of TUBA1A α-Tubulin in Forming Midline Commissures.Frontiers in cell and developmental biology · 2021Article
- A proteomic survey of microtubule-associated proteins in a R402H TUBA1A mutant mouse.PLoS genetics · 2020Article
- Candidate Genes Associated With Neurological Findings in a Patient With Trisomy 4p16.3 and Monosomy 5p15.2.Frontiers in genetics · 2020Article
- Differential requirements of tubulin genes in mammalian forebrain development.PLoS genetics · 2019Article
- Review
- TUBA1A mutations identified in lissencephaly patients dominantly disrupt neuronal migration and impair dynein activity.Human molecular genetics · 2019Article
- TAPping into the treasures of tubulin using novel protein production methods.Essays in biochemistry · 2018Review
- Distinct effects of tubulin isotype mutations on neurite growth inMolecular biology of the cell · 2017Article
- TheJournal of developmental biology · 2017Article
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6 authors at 3 institutions in 3 countries.
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Abstract
Malformations of cortical development are characteristic of a plethora of diseases that includes polymicrogyria, periventricular and subcortical heterotopia and lissencephaly. Mutations in TUBA1A and TUBB2B, each a member of the multigene families that encode alpha- and beta-tubulins, have recently been implicated in these diseases. Here we examine the defects that result from nine disease-causing mutations (I188L, I238V, P263T, L286F, V303G, L397P, R402C, 402H, S419L) in TUBA1A. We show that the expression of all the mutant proteins in vitro results in the generation of tubulin heterodimers in varying yield and that these can co-polymerize with microtubules in vitro. We identify several kinds of defects that result from these mutations. Among these are various defects in the chaperone-dependent pathway leading to de novo tubulin heterodimer formation. These include a defective interaction with the chaperone prefoldin, a reduced efficiency in the generation of productive folding intermediates as a result of inefficient interaction with the cytosolic chaperonin, CCT, and, in several cases, a failure to stably interact with TBCB, one of five tubulin-specific chaperones that act downstream of CCT in the tubulin heterodimer assembly pathway. Other defects include structural instability in vitro, diminished stability in vivo, a compromised ability to co-assemble with microtubules in vivo and a suppression of microtubule growth rate in the neurites (but not the soma) of cultured neurons. Our data are consistent with the notion that some mutations in TUBA1A result in tubulin deficit, whereas others reflect compromised interactions with one or more MAPs that are essential to proper neuronal migration.
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