Phosphorylation controls autoinhibition of cytoplasmic linker protein-170

Ho-Sup Lee, Yulia A Komarova*, Elena S Nadezhdina, Rana Anjum, John G Peloquin, Joseph M Schober, Oana Danciu, Jeffrey van Haren, Niels Galjart, Steven P Gygi, Anna Akhmanova, Gary G Borisy

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

38 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2661-2673
Number of pages13
JournalMolecular Biology of the Cell
Issue number15
Publication statusPublished - 1 Aug 2010

Research programs

  • EMC MGC-02-13-02


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