The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules.

Maruta, Hidenori; Greer, Karen L.; Rosenbaum, Joel L.

doi:10.1083/jcb.103.2.571

Cited by 237 publications

(188 citation statements)

References 18 publications

(28 reference statements)

Supporting

Mentioning

173

Contrasting

Unclassified

Order By: Relevance

“…4D). In addition, we found that αTAT1 does not acetylate tubulin dimers as efficiently as it does intact microtubules, consistent with previous αTAT1 studies (18,19) (Fig. 4E, blue).…”

Section: Resultssupporting

confidence: 80%

“…There are several potential mechanisms for how αTAT1 may access the acetylation site on the inside of the microtubule lumen: by copolymerization with tubulin at growing microtubule plus-ends (15), by transient openings in the lattice during microtubule breathing (13,16,17), or by microtubule end-entry (12,18). Copolymerization is not likely to be the primary mechanism for αTAT1 access, because stable microtubules are acetylated, and because αTAT1 is more active on polymerized microtubules than on free tubulin dimers (12,13,(19)(20)(21)(22)(23)(24)(25). Conversely, the other modes of access are possible (12,13,18).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mechanism of microtubule lumen entry for the α-tubulin acetyltransferase enzyme αTAT1

Coombes

Yamamoto

McClellan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

113

View full text Add to dashboard Cite

Microtubules are structural polymers inside of cells that are subject to posttranslational modifications. These posttranslational modifications create functionally distinct subsets of microtubule networks in the cell, and acetylation is the only modification that takes place in the hollow lumen of the microtubule. Although it is known that the α-tubulin acetyltransferase (αTAT1) is the primary enzyme responsible for microtubule acetylation, the mechanism for how αTAT1 enters the microtubule lumen to access its acetylation sites is not well understood. By performing biochemical assays, fluorescence and electron microscopy experiments, and computational simulations, we found that αTAT1 enters the microtubule lumen through the microtubule ends, and through bends or breaks in the lattice. Thus, microtubule structure is an important determinant in the acetylation process. In addition, once αTAT1 enters the microtubule lumen, the mobility of αTAT1 within the lumen is controlled by the affinity of αTAT1 for its acetylation sites, due to the rapid rebinding of αTAT1 onto highly concentrated α-tubulin acetylation sites. These results have important implications for how acetylation could gradually accumulate on stable subsets of microtubules inside of the cell.microtubule | acetylation | biophysics | microscopy | modeling

show abstract

“…4D). In addition, we found that αTAT1 does not acetylate tubulin dimers as efficiently as it does intact microtubules, consistent with previous αTAT1 studies (18,19) (Fig. 4E, blue).…”

Section: Resultssupporting

confidence: 80%

mentioning

confidence: 99%

Mechanism of microtubule lumen entry for the α-tubulin acetyltransferase enzyme αTAT1

Coombes

Yamamoto

McClellan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

113

View full text Add to dashboard Cite

show abstract

“…4a,b). Physiologically, acetylation of tubulin occurs preferentially on polymerized MT 33 , whereas deacetylation of a-tubulin by HDAC6 is thought to occur when a-tubulin is in a heterodimeric state 34 . Therefore, HDAC6 might be a target of Ab, translating its effect on tubulin acetylation.…”

Section: Ab Increases Mt Dynamics and Increases Acetylated Tubulinmentioning

confidence: 99%

HDAC6 and RhoA are novel players in Abeta-driven disruption of neuronal polarity

et al. 2015

View full text Add to dashboard Cite

Maintenance of neuronal polarity and regulation of cytoskeletal dynamics are vital during development and to uphold synaptic activity in neuronal networks. Here we show that soluble b-amyloid (Ab) disrupts actin and microtubule (MT) dynamics via activation of RhoA and inhibition of histone deacetylase 6 (HDAC6) in cultured hippocampal neurons. The contact of Ab with the extracellular membrane promotes RhoA activation, leading to growth cone collapse and neurite retraction, which might be responsible for hampered neuronal pathfinding and migration in Alzheimer's disease (AD). The inhibition of HDAC6 by Ab increases the level of heterodimeric acetylated tubulin and acetylated tau, both of which have been found altered in AD. We also find that the loss of HDAC6 activity perturbs the integrity of axon initial segment (AIS), resulting in mislocalization of ankyrin G and increased MT instability in the AIS concomitant with loss of polarized localization of tau and impairment of action potential firing.

show abstract

“…Acetylation of tubulin has been shown to occur preferentially on preformed microtubules, rather than on free tubulin dimers (Maruta et al, 1986;Black et al, 1989). The site of acetylation then must be accessible on the surface of microtubules.…”

Section: Discussionmentioning

confidence: 99%

Microtubule-associated proteins-dependent colchicine stability of acetylated cold-labile brain microtubules from the Atlantic cod, Gadus morhua.

Billger

Strömberg

Wallin

1991

The Journal of Cell Biology

View full text Add to dashboard Cite

Abstract. Assembly of brain microtubule proteins isolated from the Atlantic cod, Gadus morhua, was found to be much less sensitive to colchicine than assembly of bovine brain microtubules, which was completely inhibited by low colchicine concentrations (10 #M). The degree of disassembly by colchicine was also less for cod microtubules. The lack of colchicine effect was not caused by a lower affinity of colchicine to cod tubulin, as colchicine bound to cod tubulin with a dissociation constant, Kd, and a binding ratio close to that of bovine tubulin.Cod brain tubulin was highly acetylated and mainly detyrosinated, as opposed to bovine tubulin. When cod tubulin, purified by means of phosphocellulose chromatography, was assembled by addition of DMSO in the absence of microtubule-associated proteins (MAPs), the microtubules became sensitive to low concentrations of colchicine. They were, however, slightly more stable to disassembly, indicating that posttranslational modifications induce a somewhat increased stability to colchicine. The stability was mainly MAPs dependent, as it increased markedly in the presence of MAPs. The stability was not caused by an extremely large amount of cod MAPs, since there were slightly less MAPs in cod than in bovine microtubules. When "hybrid" microtubules were assembled from cod tubulin and bovine MAPs, these microtubules became less sensitive to colchicine. This was not a general effect of MAPs, since bovine MAPs did not induce a colchicine stability of microtubules assembled from bovine tubulin. We can therefore conclude that MAPs can induce colchicine stability of colchicine labile acetylated tubulin.M ICROTUBULES constitute a dynamic part of the cytoskeleton in eukaryotic cells. They can be isolated for studies in vitro, and such studies show that microtubules are built of tubulin and several microtubule-associated proteins (MAPs) ~. Microtubule proteins in vitro reflect the dynamics in vivo, in that they can be brought through cycles of assembly and disassembly. Furthermore, they may be disassembled by several microtubule-disrupting agents, such as cold, Ca ~+ or colchicine.Previous studies have shown that an isolated fraction of cold-labile microtubules, from brains of the Atlantic cod (Gadus morhua) exhibit atypical features, i.e., they are not broken down by calcium, and they are associated with an unusual set of MAPs (Str/~mberg et al., 1989). In addition, neurophysiological studies on cod autonomic innervation, where Part of these results have been presented in preliminary form at the 4th Meeting of the European Cytoskeletal Club, held in Lyon, France, in 1988 (Billger, M., E. Strfmberg, and M. Wallin. 1988 colchicine was employed to increase the levels of neuropeptides in autonomic ganglia cells, failed, possibly due to an ineffectiveness of colchicine to disrupt cod axonal transport (Drs. S. Holmgren and A.-C. J/Snsson, Department of Zoophysiology, Comparative Neuroscience Unit, University of G~teborg, Sweden, personal communication). This observation might indicate that ...

show abstract

The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules.

Cited by 237 publications

References 18 publications

Mechanism of microtubule lumen entry for the α-tubulin acetyltransferase enzyme αTAT1

Mechanism of microtubule lumen entry for the α-tubulin acetyltransferase enzyme αTAT1

HDAC6 and RhoA are novel players in Abeta-driven disruption of neuronal polarity

Microtubule-associated proteins-dependent colchicine stability of acetylated cold-labile brain microtubules from the Atlantic cod, Gadus morhua.

Contact Info

Product

Resources

About