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GSK3β loosens the CLASP on microtubules

GSK3β phosphorylates CLASP, changing its localization from all along microtubules (left) to exclusive binding at growing microtubule plus ends (right).

Microtubules at the leading edge of migrating epithelial cells are stable and decorated along their length by a protein called CLASP. Back in the cell body, microtubules are much more dynamic, and CLASP only binds to their growing ends. Kumar et al. reveal how a gradient of phosphorylation by GSK3β could cause this switch in CLASP's behavior.

The kinase activity of GSK3β changes from the front to back of migrating cells: low activity at the leading edge but higher in the cell body. Since expressing a highly active form of GSK3β completely removes CLASP from microtubules, Kumar et al. were interested to see whether phosphorylation could have more subtle effects on CLASP's localization.

The team identified nine sites in CLASP that could be phosphorylated by GSK3β all within a domain called MT#1 that recognizes growing microtubule ends. Although other domains are required for CLASP's binding along microtubules, phosphorylation of MT#1 was sufficient to regulate CLASP's localization: unphosphorylated CLASP bound along the length of microtubules while partial phosphorylation promoted its switch to microtubule ends. Author Torsten Wittmann thinks that increased CLASP binding at the cell front may help stabilize the microtubules by anchoring them to the cell cortex. CLASP probably links microtubules to the cortex through interactions with other proteins, like LL5b or ACF7, that bind to its C terminus; deleting CLASP's C terminus prevented stable cortical attachments from forming.

Many CLASP-stabilized microtubules cluster near focal adhesions, where the cell binds to the extracellular matrix. Wittmann now plans to investigate what these microtubules actually do: they could be involved in adhesion site turnover, or in the transport of cargo required for matrix degradation during cell migration.

References

Kumar, P., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200901042.[Abstract/Free Full Text]

bshort{at}rockefeller.edu

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GSK3β phosphorylation modulates CLASP–microtubule association and lamella microtubule attachment

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This Article Full Text (PDF, 523K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Short, B. Search for Related Content PubMed Articles by Short, B. Related Collections Related Article Social Bookmarking                            What's this?