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Mol Biol Cell. 2010 Aug 1;21(15):2661-73. doi: 10.1091/mbc.E09-12-1036. Epub 2010 Jun 2.

Phosphorylation controls autoinhibition of cytoplasmic linker protein-170.

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1
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611, USA.

Abstract

Cytoplasmic linker protein (CLIP)-170 is a microtubule (MT) plus-end-tracking protein that regulates MT dynamics and links MT plus ends to different intracellular structures. We have shown previously that intramolecular association between the N and C termini results in autoinhibition of CLIP-170, thus altering its binding to MTs and the dynactin subunit p150(Glued) (J. Cell Biol. 2004: 166, 1003-1014). In this study, we demonstrate that conformational changes in CLIP-170 are regulated by phosphorylation that enhances the affinity between the N- and C-terminal domains. By using site-directed mutagenesis and phosphoproteomic analysis, we mapped the phosphorylation sites in the third serine-rich region of CLIP-170. A phosphorylation-deficient mutant of CLIP-170 displays an "open" conformation and a higher binding affinity for growing MT ends and p150(Glued) as compared with nonmutated protein, whereas a phosphomimetic mutant confined to the "folded back" conformation shows decreased MT association and does not interact with p150(Glued). We conclude that phosphorylation regulates CLIP-170 conformational changes resulting in its autoinhibition.

PMID:
20519438
PMCID:
PMC2912352
DOI:
10.1091/mbc.E09-12-1036
[Indexed for MEDLINE]
Free PMC Article
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