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PMID:20829795

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Citation

Akella, JS, Wloga, D, Kim, J, Starostina, NG, Lyons-Abbott, S, Morrissette, NS, Dougan, ST, Kipreos, ET and Gaertig, J (2010) MEC-17 is an alpha-tubulin acetyltransferase. Nature 467:218-22

Abstract

In most eukaryotic cells, subsets of microtubules are adapted for specific functions by post-translational modifications (PTMs) of tubulin subunits. Acetylation of the epsilon-amino group of K40 on alpha-tubulin is a conserved PTM on the luminal side of microtubules that was discovered in the flagella of Chlamydomonas reinhardtii. Studies on the significance of microtubule acetylation have been limited by the undefined status of the alpha-tubulin acetyltransferase. Here we show that MEC-17, a protein related to the Gcn5 histone acetyltransferases and required for the function of touch receptor neurons in Caenorhabditis elegans, acts as a K40-specific acetyltransferase for alpha-tubulin. In vitro, MEC-17 exclusively acetylates K40 of alpha-tubulin. Disruption of the Tetrahymena MEC-17 gene phenocopies the K40R alpha-tubulin mutation and makes microtubules more labile. Depletion of MEC-17 in zebrafish produces phenotypes consistent with neuromuscular defects. In C. elegans, MEC-17 and its paralogue W06B11.1 are redundantly required for acetylation of MEC-12 alpha-tubulin, and contribute to the function of touch receptor neurons partly via MEC-12 acetylation and partly via another function, possibly by acetylating another protein. In summary, we identify MEC-17 as an enzyme that acetylates the K40 residue of alpha-tubulin, the only PTM known to occur on the luminal surface of microtubules.

Links

PubMed PMC2938957 Online version:10.1038/nature09324

Keywords

Acetylation; Acetyltransferases/metabolism; Animals; Caenorhabditis elegans/enzymology; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/metabolism; Cell Line; Dipodomys; Humans; Protozoan Proteins/genetics; Protozoan Proteins/metabolism; Tetrahymena/metabolism; Touch; Tubulin/chemistry; Tubulin/metabolism; Zebrafish/embryology; Zebrafish/metabolism; Zebrafish Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:ATAT1

enables

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:ATAT1

involved_in

GO:0001966: thigmotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00093292

P

Seeded From UniProt

complete

CAEEL:ATAT1

involved_in

GO:0001966: thigmotaxis

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00021059

P

Seeded From UniProt

complete

CAEEL:ATAT1

involved_in

GO:0006473: protein acetylation

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00021059

P

Seeded From UniProt

complete

CAEEL:ATAT1

enables

GO:0004468: lysine N-acetyltransferase activity, acting on acetyl phosphate as donor

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q22XZ3

F

Seeded From UniProt

complete

CAEEL:ATAT1

colocalizes_with

GO:0005874: microtubule

ECO:0000305: curator inference used in manual assertion

GO:0019799

C

Seeded From UniProt

complete

CAEEL:TBA3

involved_in

GO:0001966: thigmotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00144146

P

Seeded From UniProt

complete

CAEEL:TBA3

located_in

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:TBA3

located_in

GO:0043025: neuronal cell body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

TETTS:ATAT

enables

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

TETTS:ATAT

involved_in

GO:0070507: regulation of microtubule cytoskeleton organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:ATAT2

enables

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:ATAT2

involved_in

GO:0001966: thigmotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00093564

P

Seeded From UniProt

complete

CAEEL:ATAT2

involved_in

GO:0001966: thigmotaxis

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003178

P

Seeded From UniProt

complete

CAEEL:ATAT2

involved_in

GO:0006473: protein acetylation

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003178

P

Seeded From UniProt

complete

CAEEL:ATAT2

enables

GO:0004468: lysine N-acetyltransferase activity, acting on acetyl phosphate as donor

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q22XZ3

F

Seeded From UniProt

complete

HUMAN:ATAT

enables

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:ATAT

enables

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:ATAT

involved_in

GO:0071929: alpha-tubulin acetylation

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101007-1

P

Seeded From UniProt

complete

MOUSE:ATAT

enables

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

TETTH:Q22XZ3

GO:0000062: acyl-CoA binding

ECO:0000314:

F

Figure 5a: the acetylation of alpha-tubulin in this assay was dependent on acetyl COA.

complete
CACAO 3597

TETTH:Q22XZ3

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000315:

F

Figure 1. Disrupted MEC17 showed a loss of acetyl-K40, as inferred from immunofluorescence with mAbs specific for acetyl-K40 on α-tubulin.

complete
CACAO 3596

TETTH:Q22XZ3

enables

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

TETTH:Q22XZ3

involved_in

GO:0070507: regulation of microtubule cytoskeleton organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:Q23192

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000316:

UniProtKB:O45100


F

Figure 2 shows that this gene, along with mec-17, regulated the acetylation of alpha tubulin (as determined by antibody 6-11B-1

complete
CACAO 3599

CAEEL:Q23192

involved_in

GO:0001966: thigmotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00093564

P

Seeded From UniProt

complete

CAEEL:Q23192

involved_in

GO:0001966: thigmotaxis

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003178

P

Seeded From UniProt

complete

CAEEL:Q23192

enables

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:Q23192

involved_in

GO:0006473: protein acetylation

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003178

P

Seeded From UniProt

complete

CAEEL:Q23192

enables

GO:0004468: lysine N-acetyltransferase activity, acting on acetyl phosphate as donor

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q22XZ3

F

Seeded From UniProt

complete

CAEEL:O45100

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000315:

F

Figure 2. Along with W06B11.1, MEC-17 acetylates alpha tubulin. This was determined by an antibody-binding assay. Mutant C. elegans without W06B11.1 and MEC-17 did not display alpha-tubulin acetylation.

complete
CACAO 3598

CAEEL:O45100

colocalizes_with

GO:0005874: microtubule

ECO:0000305: curator inference used in manual assertion

GO:0019799

C

Seeded From UniProt

complete

CAEEL:O45100

enables

GO:0004468: lysine N-acetyltransferase activity, acting on acetyl phosphate as donor

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q22XZ3

F

Seeded From UniProt

complete

CAEEL:O45100

involved_in

GO:0006473: protein acetylation

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00021059

P

Seeded From UniProt

complete

CAEEL:O45100

involved_in

GO:0001966: thigmotaxis

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00021059

P

Seeded From UniProt

complete

CAEEL:O45100

enables

GO:0019799: tubulin N-acetyltransferase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:O45100

involved_in

GO:0001966: thigmotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00093292

P

Seeded From UniProt

complete


See also

References

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