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PMID:22493317

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Citation

Backer, CB, Gutzman, JH, Pearson, CG and Cheeseman, IM (2012) CSAP localizes to polyglutamylated microtubules and promotes proper cilia function and zebrafish development. Mol. Biol. Cell 23:2122-30

Abstract

The diverse populations of microtubule polymers in cells are functionally distinguished by different posttranslational modifications, including polyglutamylation. Polyglutamylation is enriched on subsets of microtubules including those found in the centrioles, mitotic spindle, and cilia. However, whether this modification alters intrinsic microtubule dynamics or affects extrinsic associations with specific interacting partners remains to be determined. Here we identify the microtubule-binding protein centriole and spindle-associated protein (CSAP), which colocalizes with polyglutamylated tubulin to centrioles, spindle microtubules, and cilia in human tissue culture cells. Reducing tubulin polyglutamylation prevents CSAP localization to both spindle and cilia microtubules. In zebrafish, CSAP is required for normal brain development and proper left-right asymmetry, defects that are qualitatively similar to those reported previously for depletion of polyglutamylation-conjugating enzymes. We also find that CSAP is required for proper cilia beating. Our work supports a model in which polyglutamylation can target selected microtubule-associated proteins, such as CSAP, to microtubule subpopulations, providing specific functional capabilities to these populations.

Links

PubMed PMC3364176 Online version:10.1091/mbc.E11-11-0931

Keywords


Significance

Annotations

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

HUMAN:CCSAP

located_in

GO:0005819: spindle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCSAP

located_in

GO:0005929: cilium

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCSAP

located_in

GO:0005814: centriole

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCSAP

located_in

GO:0036064: ciliary basal body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCSAP

located_in

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCSAP

located_in

GO:0005930: axoneme

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCSAP

located_in

GO:0035869: ciliary transition zone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0048666: neuron development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0007507: heart development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0007420: brain development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:CCSAP

located_in

GO:0036064: ciliary basal body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0060296: regulation of cilium beat frequency involved in ciliary motility

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0045995: regulation of embryonic development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0060548: negative regulation of cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0045930: negative regulation of mitotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0061371: determination of heart left/right asymmetry

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0007420: brain development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120611-2

P

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0003341: cilium movement

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120611-2

P

Seeded From UniProt

complete

DANRE:CCSAP

involved_in

GO:0061371: determination of heart left/right asymmetry

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120611-2

P

Seeded From UniProt

complete


See also

References

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