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*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

81 Citaten (Scopus)


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.

Originele taal-2English
Pagina's (van-tot)4189-4202
Aantal pagina's14
TijdschriftEMBO Journal
Nummer van het tijdschrift19
StatusPublished - 3-okt-2007

Citeer dit