A common cofilin activity cycle in invasive tumor cells and inflammatory cells
Open Access
- 1 February 2009
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 122 (3), 305-311
- https://doi.org/10.1242/jcs.031146
Abstract
In many cell types, the formation of membrane protrusions and directional migration depend on the spatial and temporal regulation of the actin-binding protein cofilin. Cofilin, which is important for the regulation of actin-polymerization initiation, increases the number of actin free barbed ends through three mechanisms: its intrinsic actin-nucleation activity; binding and severing of existing actin filaments; and recycling actin monomers from old filaments to new ones through its actin-depolymerization activity. The increase in free barbed ends that is caused by cofilin initiates new actin polymerization, which can be amplified by the actin-nucleating ARP2/3 complex. Interestingly, different cell systems seem to have different mechanisms of activating cofilin. The initial activation of cofilin in mammary breast tumors is dependent on PLCγ, whereas cofilin activation in neutrophils is additionally dependent on dephosphorylation, which is promoted through Rac2 signaling. Although the literature seems to be confusing and inconsistent, we propose that all of the data can be explained by a single activity-cycle model. In this Opinion, we give an overview of cofilin activation in both tumor cells and inflammatory cells, and demonstrate how the differences in cofilin activation that are observed in various cell types can be explained by different starting points in this single common activity cycle.Keywords
This publication has 66 references indexed in Scilit:
- WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cellsThe Journal of cell biology, 2008
- Arp2/3 complex interactions and actin network turnover in lamellipodiaThe EMBO Journal, 2008
- EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cellsThe Journal of cell biology, 2007
- Cofilin determines the migration behavior and turning frequency of metastatic cancer cellsThe Journal of cell biology, 2007
- Rac1 and Rac2 differentially regulate actin free barbed end formation downstream of the fMLP receptorThe Journal of cell biology, 2007
- The many faces of actin: matching assembly factors with cellular structuresNature, 2007
- Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilinThe EMBO Journal, 2007
- BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilinThe Journal of cell biology, 2007
- The cofilin pathway in breast cancer invasion and metastasisNature Reviews Cancer, 2007
- The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumorsThe Journal of cell biology, 2006