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

Li Han, Matthias B. Stope, Maider Lopez de Jesus, Paschal A. Oude Weernink, Martina Urban, Thomas Wieland, Dieter Rosskopf, Kensaku Mizuno, Karl H. Jakobs, Martina Schmidt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

81 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 14-3-3 zeta 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 14-3-3 zeta, 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 - 3-Oct-2007

Keywords

  • cofilin
  • LIM-kinase1
  • phospholipase D
  • slingshot
  • 14-3-3
  • MUSCARINIC ACETYLCHOLINE-RECEPTOR
  • STRESS FIBER FORMATION
  • PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE
  • ACTIN DYNAMICS
  • LIM KINASE
  • CYCLIC-AMP
  • REGULATES COFILIN
  • COUPLED RECEPTORS
  • EPITHELIAL-CELLS
  • MAMMALIAN-CELLS

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