ArticleMolecular biology of the cell2008
A pachygyria-causing alpha-tubulin mutation results in inefficient cycling with CCT and a deficient interaction with TBCB.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- A unified mechanism for tubulin cofactors catalyzing α/β-tubulin biogenesis and degradation.Science advances · 2026Article
- Understanding molecular mechanisms and predicting phenotypic effects of pathogenic tubulin mutations.PLoS computational biology · 2022Article
- The molecular biology of tubulinopathies: Understanding the impact of variants on tubulin structure and microtubule regulation.Frontiers in cellular neuroscience · 2022Review
- Loss-of-Function Plays a Major Role in Early Neurogenesis of Tubulin α-1 A (TUBA1A) Mutation-Related Brain Malformations.Molecular neurobiology · 2021Article
- Bridging the Gap: The Importance of TUBA1A α-Tubulin in Forming Midline Commissures.Frontiers in cell and developmental biology · 2021Article
- Microtubule dynamics at low temperature: evidence that tubulin recycling limits assembly.Molecular biology of the cell · 2020Article
- The role of the molecular chaperone CCT in protein folding and mediation of cytoskeleton-associated processes: implications for cancer cell biology.Cell stress & chaperones · 2019Review
- Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation.Brain sciences · 2018Article
- TheJournal of developmental biology · 2017Article
- HILI destabilizes microtubules by suppressing phosphorylation and Gigaxonin-mediated degradation of TBCB.Scientific reports · 2017Article
- Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability.Human molecular genetics · 2017Article
- In vitro characterization of neurite extension using induced pluripotent stem cells derived from lissencephaly patients with TUBA1A missense mutations.Molecular brain · 2016Article
- Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type.American journal of human genetics · 2015Article
- Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS.Neuron · 2014Article
- Tubulin-specific chaperones: components of a molecular machine that assembles the α/β heterodimer.Methods in cell biology · 2013Article
- Drosophila tubulin-binding cofactor B is required for microtubule network formation and for cell polarity.Molecular biology of the cell · 2012Article
- Faithful chaperones.Cellular and molecular life sciences : CMLS · 2011Review
- Phenotypic spectrum of the tubulin-related disorders and functional implications of disease-causing mutations.Current opinion in genetics & development · 2011Review
- Role of cytoskeletal abnormalities in the neuropathology and pathophysiology of type I lissencephaly.Acta neuropathologica · 2011Review
- Defective adult oligodendrocyte and Schwann cell development, pigment pattern, and craniofacial morphology in puma mutant zebrafish having an alpha tubulin mutation.Developmental biology · 2010Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The agyria (lissencephaly)/pachygyria phenotypes are catastrophic developmental diseases characterized by abnormal folds on the surface of the brain and disorganized cortical layering. In addition to mutations in at least four genes--LIS1, DCX, ARX and RELN--mutations in a human alpha-tubulin gene, TUBA1A, have recently been identified that cause these diseases. Here, we show that one such mutation, R264C, leads to a diminished capacity of de novo tubulin heterodimer formation. We identify the mechanisms that contribute to this defect. First, there is a reduced efficiency whereby quasinative alpha-tubulin folding intermediates are generated via ATP-dependent interaction with the cytosolic chaperonin CCT. Second, there is a failure of CCT-generated folding intermediates to stably interact with TBCB, one of the five tubulin chaperones (TBCA-E) that participate in the pathway leading to the de novo assembly of the tubulin heterodimer. We describe the behavior of the R264C mutation in terms of its effect on the structural integrity of alpha-tubulin and its interaction with TBCB. In spite of its compromised folding efficiency, R264C molecules that do productively assemble into heterodimers are capable of copolymerizing into dynamic microtubules in vivo. The diminished production of TUBA1A tubulin in R264C individuals is consistent with haploinsufficiency as a cause of the disease phenotype.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.