A pachygyria-causing alpha-tubulin mutation results in inefficient cycling with CCT and a deficient interaction with TBCB

Molecular Biology of the Cell
Guoling TianNicholas J Cowan

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 ...Continue Reading

References

Jan 1, 1992·Cell Motility and the Cytoskeleton·J C Zabala, N J Cowan
Sep 1, 1985·The Journal of Cell Biology·S A LewisN J Cowan
Jun 1, 1995·Neuropediatrics·W B Dobyns, C L Truwit
Oct 13, 1995·The Journal of Biological Chemistry·G TianN J Cowan
May 18, 1995·Nature·G TianN J Cowan
Jul 26, 1996·Cell·G TianN J Cowan
Aug 1, 1996·Neurology·W B DobynsC L Truwit
Feb 16, 1999·Cell·E NogalesK H Downing
Apr 20, 1999·The Journal of Cell Biology·W J HansenW J Welch
Apr 6, 2000·Human Molecular Genetics·T SapirO Reiner
Nov 1, 2000·Nature Cell Biology·N E FaulknerR B Vallee
Mar 13, 2002·The Journal of Cell Biology·Chin-Yin TaiRichard B Vallee
Sep 11, 2002·The Journal of Biological Chemistry·Songlin LiMing Luo
Oct 22, 2002·Nature Genetics·Ruti ParvariUNKNOWN HRD/Autosomal Recessive Kenny-Caffey Syndrome Consortium
Oct 22, 2002·Nature Genetics·Natalia MartinJean-Louis Guénet
Nov 26, 2002·Current Biology : CB·Dan Szymanski
May 14, 2003·Trends in Cell Biology·Pedro CarvalhoDavid Pellman
Nov 20, 2003·Nature Neuroscience·Jilin BaiJoseph J LoTurco
Feb 7, 2004·The EMBO Journal·Amos GdalyahuOrly Reiner
Jun 18, 2004·Molecular Cell·Carolyn A MooresRonald A Milligan
Sep 15, 2004·The Journal of Biological Chemistry·Betsy L LytleBrian F Volkman
Nov 3, 2004·Trends in Cell Biology·Christoph SpiessJudith Frydman
Apr 16, 2005·Molecular and Cellular Biology·Ratna K VadlamudiRakesh Kumar
Sep 8, 2005·The Journal of Cell Biology·Jin-Wu TsaiRichard B Vallee
Sep 15, 2005·The Journal of Cell Biology·Mary E Hatten
Mar 8, 2006·The European Journal of Neuroscience·Fiona FrancisJamel Chelly

❮ Previous
Next ❯

Citations

Jun 10, 2011·Cellular and Molecular Life Sciences : CMLS·Ewa Szolajska, Jadwiga Chroboczek
Nov 4, 2010·Acta Neuropathologica·Gaëlle FriocourtAnnie Laquerrière
May 26, 2009·Nature Genetics·Xavier Hubert JaglinJamel Chelly
Aug 3, 2012·Molecular Biology of the Cell·Alexandre D BaffetAntoine Guichet
Feb 2, 2010·Trends in Biochemical Sciences·Victor F LundinPeter C Stirling
Dec 26, 2016·Human Molecular Genetics·Martin W BreussJoseph G Gleeson
May 12, 2009·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·John Gardiner, Jan Marc
Oct 24, 2017·Journal of Developmental Biology·Jayne AikenJeffrey K Moore
Mar 23, 2017·Journal of Cell Science·Sudarshan GadadharCarsten Janke
Mar 31, 2009·Molecular Neurobiology·Orly Reiner, Tamar Sapir
Mar 28, 2020·Molecular Biology of the Cell·Gabriella Li, Jeffrey K Moore
Aug 9, 2018·Brain Sciences·Jennifer F GardnerAndrew E Fry
Oct 30, 2009·Trends in Genetics : TIG·Xavier H Jaglin, Jamel Chelly

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.