Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin

Li Han, Matthias B. Stope, Maider López De Jesús, Paschal A. Oude Weernink, Martina Urban, Thomas Wieland, Dieter Rosskopf, Kensaku Mizuno, Karl H. Jakobs, Martina Schmidt

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78 Citations (Scopus)

Abstract

The activity state of cofilin, which controls actin dynamics, is driven by a phosphorylation-dephosphorylation cycle. Phosphorylation of cofilin by LIM-kinases results in its inactivation, a process supported by 14-3-3ζ and reversed by dephosphorylation by slingshot phosphatases. Here we report on a novel cellular function for the phosphorylation-dephosphorylation cycle of cofilin. We demonstrate that muscarinic receptor-mediated stimulation of phospholipase D1 (PLD1) is controlled by LIM-kinase, slingshot phosphatase as well as 14-3-3ζ, and requires phosphorylatable cofilin. Cofilin directly and specifically interacts with PLD1 and upon phosphorylation by LIM-kinase1, stimulates PLD1 activity, an effect mimicked by phosphorylation-mimic cofilin mutants. The interaction of cofilin with PLD1 is under receptor control and encompasses a PLD1-specific fragment (aa 585-712). Expression of this fragment suppresses receptor-induced cofilin-PLD1 interaction as well as PLD stimulation and actin stress fiber formation. These data indicate that till now designated inactive phospho-cofilin exhibits an active cellular function, and suggest that phospho-cofilin by its stimulatory effect on PLD1 may control a large variety of cellular functions.

Original languageEnglish
Pages (from-to)4189-4202
Number of pages14
JournalEMBO Journal
Volume26
Issue number19
DOIs
Publication statusPublished - 2007 Oct 3

Keywords

  • 14-3-3
  • Cofilin
  • LIM-kinase1
  • Phospholipase D
  • Slingshot

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Han, L., Stope, M. B., De Jesús, M. L., Oude Weernink, P. A., Urban, M., Wieland, T., Rosskopf, D., Mizuno, K., Jakobs, K. H., & Schmidt, M. (2007). Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin. EMBO Journal, 26(19), 4189-4202. https://doi.org/10.1038/sj.emboj.7601852