CSAP localizes to polyglutamylated microtubules and promotes proper cilia function and zebrafish development

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, wh...

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Bibliographic Details
Published in:Molecular biology of the cell 2012-06, Vol.23 (11), p.2122-2130
Main Authors: Backer, Chelsea B, Gutzman, Jennifer H, Pearson, Chad G, Cheeseman, Iain M
Format: Article
Language:English
Subjects:
Animals
Body Patterning - genetics
Brain - embryology
Brain - metabolism
Centrioles - metabolism
Cilia - metabolism
Embryo, Nonmammalian - metabolism
Gene Expression Regulation, Developmental
HeLa Cells
Humans
Microtubule-Associated Proteins - metabolism
Microtubules - metabolism
Neurons - cytology
Neurons - metabolism
Polyglutamic Acid - metabolism
Protein Transport
Spindle Apparatus - metabolism
Zebrafish - embryology
Zebrafish - genetics
Zebrafish - metabolism
Zebrafish Proteins - metabolism
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E11-11-0931