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 language | English |
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Pages (from-to) | 4189-4202 |
Number of pages | 14 |
Journal | EMBO Journal |
Volume | 26 |
Issue number | 19 |
DOIs | |
Publication status | Published - 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