Article
- The EMBO Journal (2007) 26, 4189 - 4202
- doi:10.1038/sj.emboj.7601852
Published online: 13 September 2007
Subject Category:
Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin
Li Han1,ab, Matthias B Stope1,a, Maider López de Jesús1,a, Paschal A Oude Weernink1, Martina Urban1, Thomas Wieland2, Dieter Rosskopf1, Kensaku Mizuno3, Karl H Jakobs1 and Martina Schmidt1,4
- Institut für Pharmakologie, Universitätsklinikum Essen, Essen, Germany
- Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany
- Department of Biomolecular Sciences, Graduate School of Life Sciences, Sendai, Miyagi, Japan
- Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands
Correspondence to:
Martina Schmidt, Department of Molecular Pharmacology, University of Groningen, A. Deusinglaan 1, Groningen 9713 AV, The Netherlands. Tel.: +31 50 363 3322; Fax: +31 50 363 6908; E-mail: m.schmidt@rug.nl
aThese authors contributed equally to this work
bPresent address: Department of Infection Control, Chinese Military Institute of Disease Control & Prevention, Beijing 100071, China
Received 6 September 2006; Accepted 2 August 2007
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
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, 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.
Keywords:
- cofilin,
- LIM-kinase1,
- phospholipase D,
- slingshot,
- 14-3-3
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
Actin-binding proteins take the reins in growth cones
Nature Reviews Neuroscience Review (01 Feb 2008)
RESEARCH
Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics
Nature Cell Biology Article (01 Jan 2005)
Interplay between components of a novel LIM kinase?slingshot phosphatase complex regulates cofilin
The EMBO Journal Article (09 Feb 2005)
Mitochondrial translocation of cofilin is an early step in apoptosis induction
Nature Cell Biology Letter (01 Dec 2003)
