GSK33 phosphorylation modulates CLASP-microtubule association and lamella microtubule attachment

Praveen Kumar, Karen S. Lyle, Sarah Gierke, Alexandre Matov, Gaudenz Danuser, Torsten Wittmann

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Polarity of the microtubule (MT) cytoskeleton is essential for many cell functions. Cytoplasmic linker-associated proteins (CLASPs) are MT-associated proteins thought to organize intracellular MTs and display a unique spatio- temporal regulation. In migrating epithelial cells, CLASPs track MT plus ends in the cell body but bind along MTs in the lamella. In this study, we demonstrate that glycogen synthase kinase 3β (GSK3β) directly phosphorylates CLASPs at multiple sites in the domain required for MT plus end tracking. Although complete phosphorylation disrupts both plus end tracking and association along lamella MTs, we show that partial phosphorylation of the identified GSK3β motifs determines whether CLASPs track plus ends or associate along MTs. In addition, we find that expression of constitutively active GSK3β destabilizes lamella MTs by disrupting lateral MT interactions with the cell cortex. GSK3β -induced lamella MT destabilization was partially rescued by expression of CLASP2 with mutated phosphorylation sites. This indicates that CLASP-mediated stabilization of peripheral MTs, which likely occurs in the vicinity of focal adhesions, may be regulated by local GSK3β inactivation.

Original languageEnglish (US)
Pages (from-to)895-908
Number of pages14
JournalJournal of Cell Biology
Volume184
Issue number6
DOIs
StatePublished - Mar 23 2009

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Glycogen Synthase Kinase 3
Microtubule-Associated Proteins
Microtubules
Phosphorylation
Proteins
Focal Adhesions
Cytoskeleton
Cell Communication
Epithelial Cells

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

GSK33 phosphorylation modulates CLASP-microtubule association and lamella microtubule attachment. / Kumar, Praveen; Lyle, Karen S.; Gierke, Sarah; Matov, Alexandre; Danuser, Gaudenz; Wittmann, Torsten.

In: Journal of Cell Biology, Vol. 184, No. 6, 23.03.2009, p. 895-908.

Research output: Contribution to journalArticle

Kumar, Praveen ; Lyle, Karen S. ; Gierke, Sarah ; Matov, Alexandre ; Danuser, Gaudenz ; Wittmann, Torsten. / GSK33 phosphorylation modulates CLASP-microtubule association and lamella microtubule attachment. In: Journal of Cell Biology. 2009 ; Vol. 184, No. 6. pp. 895-908.
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AU - Wittmann, Torsten

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