Phosphorylation of CLASP2 by GSK-3β regulates its interaction with IQGAP1, EB1 and microtubules

Takashi Watanabe, Jun Noritake, Mai Kakeno, Toshinori Matsui, Takumi Harada, Shujie Wang, Norimichi Itoh, Kazuhide Sato, Kenji Matsuzawa, Akihiro Iwamatsu, Niels Galjart, Kozo Kaibuchi

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)

Abstract

Polarised cell migration is required for various cell behaviours and functions. Actin and microtubules are coupled structurally and distributed asymmetrically along the front-rear axis of migrating cells. CLIP-associating proteins (CLASPs) accumulate near the ends of microtubules at the front of migrating cells to control microtubule dynamics and cytoskeletal coupling. Regional inhibition of GSK-3β is responsible for this asymmetric distribution of CLASPs. However, it is not known how GSK-3β regulates the activity of CLASPs for linkage between actin and microtubules. Here we identified IQGAP1, an actin-binding protein, as a novel CLASP-binding protein. GSK-3β directly phosphorylates CLASP2 at Ser533 and Ser537 within the region responsible for the IQGAP1 binding. Phosphorylation of CLASP2 results in the dissociation of CLASP2 from IQGAP1, EB1 and microtubules. At the leading edges of migrating fibroblasts, CLASP2 near microtubule ends partially colocalises with IQGAP1. Expression of active GSK-3β abrogates the distribution of CLASP2 on microtubules, but not that of a nonphosphorylatable CLASP2 mutant. The phosphorylated CLASP2 does not accumulate near the ends of microtubules at the leading edges. Thus, phosphorylation of CLASP2 by GSK-3β appears to control the regional linkage of microtubules to actin filaments through IQGAP1 for cell migration.

Original languageEnglish
Pages (from-to)2969-2979
Number of pages11
JournalJournal of cell science
Volume122
Issue number16
DOIs
Publication statusPublished - 15-08-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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