skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure

Journal Article · · Molecular Biology of the Cell
 [1];  [2];  [3];  [3];  [4]
  1. Univ. of California, Berkeley, CA (United States). Biophysics Graduate Group
  2. Univ. of California, Berkeley, CA (United States).Howard Hughes Medical Inst. Dept. of Molecular and Cell Biology
  3. Stanford Univ., CA (United States). School of Medicine. Dept. of Molecular and Cellular Physiology
  4. Univ. of California, Berkeley, CA (United States).Howard Hughes Medical Inst. Dept. of Molecular and Cell Biology; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division

Tubulin undergoes posttranslational modifications proposed to specify microtubule subpopulations for particular functions. Most of these modifications occur on the C-termini of tubulin and may directly affect the binding of microtubule-associated proteins (MAPs) or motors. Acetylation of Lys-40 on α-tubulin is unique in that it is located on the luminal surface of microtubules, away from the interaction sites of most MAPs and motors. We investigate whether acetylation alters the architecture of microtubules or the conformation of tubulin, using cryo–electron microscopy (cryo-EM). No significant changes are observed based on protofilament distributions or microtubule helical lattice parameters. Furthermore, no clear differences in tubulin structure are detected between cryo-EM reconstructions of maximally deacetylated or acetylated microtubules. Our results indicate that the effect of acetylation must be highly localized and affect interaction with proteins that bind directly to the lumen of the microtubule. We also investigate the interaction of the tubulin acetyltransferase, αTAT1, with microtubules and find that αTAT1 is able to interact with the outside of the microtubule, at least partly through the tubulin C-termini. Binding to the outside surface of the microtubule could facilitate access of αTAT1 to its luminal site of action if microtubules undergo lateral opening between protofilaments.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1625232
Journal Information:
Molecular Biology of the Cell, Vol. 25, Issue 2; ISSN 1059-1524
Publisher:
American Society for Cell BiologyCopyright Statement
Country of Publication:
United States
Language:
English

References (61)

Microtubule Structure at Improved Resolution journal July 2001
Posttranslational modifications of alpha tubulin: detyrosination and acetylation differentiate populations of interphase microtubules in cultured cells. journal April 1988
Tubulin tyrosination navigates the kinesin-1 motor domain to axons journal April 2009
A structural change in the kinesin motor protein that drives motility journal December 1999
Posttranslational Acetylation of α-Tubulin Constrains Protofilament Number in Native Microtubules journal June 2012
Microtubule Acetylation Promotes Kinesin-1 Binding and Transport journal November 2006
+TIPs: SxIPping along microtubule ends journal August 2012
UCSF Chimera?A visualization system for exploratory research and analysis journal January 2004
Luminal material in microtubules of frog olfactory axons: structure and distribution. journal August 1984
Differential trafficking of Kif5c on tyrosinated and detyrosinated microtubules in live cells journal April 2008
Diffusion inside microtubules journal August 1998
EMAN2: An extensible image processing suite for electron microscopy journal January 2007
A novel acetylation of β-tubulin by San modulates microtubule polymerization via down-regulating tubulin incorporation journal February 2011
Dysferlin Interacts with Histone Deacetylase 6 and Increases alpha-Tubulin Acetylation journal December 2011
Cytoplasmic microtubules containing acetylated alpha-tubulin in Chlamydomonas reinhardtii: spatial arrangement and properties journal July 1986
Molecular basis of the acetyltransferase activity of MEC-17 towards α-tubulin journal November 2012
The major  -tubulin K40 acetyltransferase  TAT1 promotes rapid ciliogenesis and efficient mechanosensation journal November 2010
Structural basis for the regulation of tubulin by vinblastine journal May 2005
Structure of the  -tubulin acetyltransferase,  TAT1, and implications for tubulin-specific acetylation journal October 2012
HDAC6 is a microtubule-associated deacetylase journal May 2002
Appion: An integrated, database-driven pipeline to facilitate EM image processing journal April 2009
Automated molecular microscopy: The new Leginon system journal July 2005
Atomic resolution structure of human  -tubulin acetyltransferase bound to acetyl-CoA journal October 2012
High-Resolution Model of the Microtubule journal January 1999
The iterative helical real space reconstruction method: Surmounting the problems posed by real polymers journal January 2007
The bromodomain interaction module journal May 2012
Luminal particles within cellular microtubules journal September 2006
Low resolution structure of microtubules in solution journal July 1992
Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions journal July 2009
ER sliding dynamics and ER–mitochondrial contacts occur on acetylated microtubules journal August 2010
The Human Sir2 Ortholog, SIRT2, Is an NAD+-Dependent Tubulin Deacetylase journal February 2003
The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules journal August 1986
Microtubules containing acetylated alpha-tubulin in mammalian cells in culture. journal February 1987
Structural Basis of Interprotofilament Interaction and Lateral Deformation of Microtubules journal August 2010
MEC-17 is an α-tubulin acetyltransferase journal September 2010
Chlamydomonas alpha-tubulin is posttranslationally modified in the flagella during flagellar assembly. journal July 1983
Motor-dependent microtubule disassembly driven by tubulin tyrosination journal June 2009
Visualization of cell microtubules in their native state journal January 2007
The Effect of Temperature on the Structure of Vinblastine-induced Polymers of Purified Tubulin: Detection of a Reversible Conformational Change journal December 1995
Kinesin-13s form rings around microtubules journal October 2006
Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions journal November 2011
Posttranslational glutamylation of alpha-tubulin journal January 1990
Monoclonal antibodies specific for an acetylated form of alpha-tubulin recognize the antigen in cilia and flagella from a variety of organisms. journal December 1985
Requirement for Microtubules in New Membrane Formation during Cytokinesis ofXenopusEmbryos journal February 1998
The posttranslational modification of tubulin undergoes a switch from detyrosination to acetylation as epithelial cells become polarized journal April 2011
Identification of an acetylation site of Chlamydomonas alpha-tubulin. journal August 1987
Fast Kinetics of Taxol Binding to Microtubules journal March 2003
Single Molecule Imaging Reveals Differences in Microtubule Track Selection Between Kinesin Motors journal October 2009
Elongator Controls the Migration and Differentiation of Cortical Neurons through Acetylation of α-Tubulin journal February 2009
HDAC6 Deacetylase Activity Links the Tubulin Cytoskeleton with Immune Synapse Organization journal April 2004
Chlamydomonas .alpha.-tubulin is posttranslationally modified by acetylation on the .epsilon.-amino group of a lysine journal January 1985
Tubulin in sea urchin embryonic cilia: post-translational modifications during regeneration journal April 1992
Relationship between the Golgi complex and microtubules enriched in detyrosinated or acetylated ?-tubulin: studies on cells recovering from nocodazole and cells in the terminal phase of cytokinesis journal September 1993
Microtubule Modification: Acetylation Speeds Anterograde Traffic Flow journal January 2007
CLIP-170 Highlights Growing Microtubule Ends In Vivo journal February 1999
How does taxol stabilize microtubules? journal August 1995
Tubulin acetyltransferase discovered: Ciliary role in the ancestral eukaryote expanded to neurons in metazoans journal December 2010
α-Tubulin acetylation from the inside out journal November 2012
Crystal Structures of Tubulin Acetyltransferase Reveal a Conserved Catalytic Core and the Plasticity of the Essential N Terminus* journal December 2012
Acetylation of Microtubules Influences Their Sensitivity to Severing by Katanin in Neurons and Fibroblasts journal May 2010
Luminal particles within cellular microtubules. text January 2006

Cited By (53)

Posttranslational Modifications of Tubulin and Cilia journal December 2016
ATAT1 regulates forebrain development and stress-induced tubulin hyperacetylation journal April 2019
Effects of mutating α-tubulin lysine 40 on sensory dendrite development journal January 2017
Regulation of Microtubule Disassembly by Spatially Heterogeneous Patterns of Acetylation posted_content August 2019
Histone deacetylase 3 indirectly modulates tubulin acetylation journal November 2015
Tubulin Post-Translational Modifications and Microtubule Dynamics journal October 2017
The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin journal March 2015
ATAT1-enriched vesicles promote microtubule acetylation via axonal transport journal December 2019
The inner junction complex of the cilia is an interaction hub that involves tubulin post-translational modifications journal January 2020
Regulation of microtubule disassembly by spatially heterogeneous patterns of acetylation journal January 2020
Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing α-tubulin acetylation in breast cancer journal May 2016
The Inner Junction Complex of the Cilia is an Interaction Hub that Involves Tubulin Post-translational Modifications journal February 2020
Nucleotide– and Mal3-dependent changes in fission yeast microtubules suggest a structural plasticity view of dynamics journal December 2017
Differences in Functional Expression of Connexin43 and NaV1.5 by Pan- and Class-Selective Histone Deacetylase Inhibition in Heart journal August 2018
The actin-MRTF-SRF transcriptional circuit controls tubulin acetylation via α-TAT1 gene expression journal January 2018
A Systematic Review of Suggested Molecular Strata, Biomarkers and Their Tissue Sources in ALS journal May 2019
Role of LPS-elicited signaling in triggering gastric mucosal inflammatory responses to H. pylori: modulatory effect of ghrelin journal May 2017
Effects of mutating α-tubulin lysine 40 on sensory dendrite development posted_content November 2017
Structural and functional differences between porcine brain and budding yeast microtubules journal January 2018
α-Tubulin K40 acetylation is required for contact inhibition of proliferation and cell–substrate adhesion journal June 2014
Cilium structure, assembly, and disassembly regulated by the cytoskeleton journal July 2018
Histamine and histidine decarboxylase in the olfactory system and brain of the common cuttlefish Sepia officinalis (Linnaeus, 1758) journal November 2019
The tubulin code at a glance journal March 2017
The tubulin code: Molecular components, readout mechanisms, and functions journal August 2014
MicroRNA-92a is a circadian modulator of neuronal excitability in Drosophila journal March 2017
The therapeutic hope for HDAC6 inhibitors in malignancy and chronic disease journal May 2016
The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology journal November 2019
Tubulin Acetylation Mediates Bisphenol A Effects on the Microtubule Arrays of Allium cepa and Triticum turgidum journal May 2019
Effects of α-tubulin acetylation on microtubule structure and stability journal May 2019
Tubulin acetylation protects long-lived microtubules against mechanical ageing journal February 2017
The HDAC6 Inhibitor Trichostatin A Acetylates Microtubules and Protects Axons From Excitotoxin-Induced Degeneration in a Compartmented Culture Model journal November 2018
A Case for Microtubule Vulnerability in Amyotrophic Lateral Sclerosis: Altered Dynamics During Disease journal September 2016
The Elongator subunit Elp3 is a non-canonical tRNA acetyltransferase text January 2019
The Elongator subunit Elp3 is a non-canonical tRNA acetyltransferase journal February 2019
G protein-coupled receptor kinase 5 modifies cancer cell resistance to paclitaxel journal July 2019
Cardiac microtubules in health and heart disease journal August 2019
Insights of the tubulin code in gametes and embryos: from basic research to potential clinical applications in humans† journal September 2018
Back to the tubule: microtubule dynamics in Parkinson’s disease journal September 2016
The world of protein acetylation journal October 2016
Effects of α-Tubulin K40 Acetylation and Detyrosination on Kinesin-1 Motility in a Purified System journal June 2014
The Motility of Axonemal Dynein Is Regulated by the Tubulin Code journal December 2014
Causes and Consequences of Microtubule Acetylation journal December 2017
Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS journal October 2014
Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin 2 inhibition journal August 2016
αTAT1 downregulation induces mitotic catastrophe in HeLa and A549 cells journal February 2016
Human histone deacetylase 6 shows strong preference for tubulin dimers over assembled microtubules journal September 2017
αTAT1 controls longitudinal spreading of acetylation marks from open microtubules extremities journal October 2016
A conceptual view at microtubule plus end dynamics in neuronal axons journal August 2016
TgATAT-Mediated α-Tubulin Acetylation Is Required for Division of the Protozoan Parasite Toxoplasma gondii journal February 2016
The primary cilium is a self-adaptable, integrating nexus for mechanical stimuli and cellular signaling journal November 2015
The Altered Hepatic Tubulin Code in Alcoholic Liver Disease journal September 2015
High-resolution Time-lapse Imaging and Automated Analysis of Microtubule Dynamics in Living Human Umbilical Vein Endothelial Cells journal August 2016
Expression of acetylated tubulin in the postnatal developing mouse cochlea journal August 2018

Similar Records

Effects of α-tubulin acetylation on microtubule structure and stability
Journal Article · Thu May 09 00:00:00 EDT 2019 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1625232

Genetic disruption of tubulin acetyltransferase, αTAT1, inhibits proliferation and invasion of colon cancer cells through decreases in Wnt1/β-catenin signaling
Journal Article · Sun Jan 01 00:00:00 EST 2017 · Biochemical and Biophysical Research Communications · OSTI ID:1625232

Structural and functional features of lysine acetylation of plant and animal tubulins
Journal Article · Wed Nov 15 00:00:00 EST 2017 · Cell Biology International · OSTI ID:1625232