title: A common cofilin activity cycle in invasive tumor cells and inflammatory cells.
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 PLCgamma, 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.
authors.affiliation: Department of Anatomy and Structural Biology, Gruss Lipper Center for Biophotonics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA. j.vanrheenen@niob.knaw.nl
authors.forename: Jacco
authors.initials: J
authors.lastname: van Rheenen
authors.forename: John
authors.initials: J
authors.lastname: Condeelis
authors.forename: Michael
authors.initials: M
authors.lastname: Glogauer
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002633:Chemotaxis / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate; D011494:Protein Kinases; D051966:Phospholipase C gamma