%0 Journal Article
%T Focus on ADF/Cofilin: Beyond Actin Cytoskeletal Regulation
%A Cheng-Han Tsai
%A Yi-Jang Lee
%J ISRN Cell Biology
%D 2012
%R 10.5402/2012/597876
%X Actin depolymerizing factor (ADF)/cofilin, an actin-binding protein ubiquitously expressed in a variety of organisms, is required for regulation of actin dynamics. The activity of ADF/cofilin is dependent on serine 3 phosphorylation by LIM kinase (LIMK), which is regulated by the Rho small GTPase signaling pathway. ADF/cofilin is strongly associated with several important cell biological functions, including cell cycle, morphological maintenance, and locomotion. These functions affect several biological events, including embryogenesis, oncology, nephropathy, and neurodegenerations. Here, we focus on the biochemical and pathophysiological role of ADF/cofilin in mammals. 1. Introduction ADF/cofilin has been reported to be involved in several cellular functions via regulation of actin dynamics. For instance, ADF/cofilin is required for actin reorganization at the contractile ring for cytokinesis and is essential for cell cycle progression. ADF/cofilin regulates actin dynamics through a depolymerization or severing of actin filaments. The only known mechanism for regulating the activity of ADF/cofilin activity is protein phosphorylation. ADF/cofilin becomes inactive when it is phosphorylated at serine 3 residue by LIM kinase (LIMK) or testis-specific kinase (TESK) 1 and 2 [1¨C3]. For LIMK, a series of signal transduction pathway for ADF/cofilin activity is primarily controlled by Rho family of small GTPase. Cells stimulated by growth factors lead to activation of the receptor tyrosine kinase (RTK) that recruits Rho small GTPase and Rho-associated protein kinase (ROCK) to phosphorylate LIM kinase and subsequent ADF/cofilin [4]. Also, dephosphorylation of ADF/cofilin is mediated by slingshot (SSH) phosphatase, chronophin (CIN) phosphatase, and protein phosphatase 1 and 2A (PP1 and PP2A) [5]. In addition to protein phosphorylation, the activity of ADF/cofilin is also regulated by intracellular pH and its association with phosphatidyl inositol bisphosphate (PIP2) [6]. Recent studies have shown that the activity of ADF/cofilin is increased at the telophase of mitosis to regulate the dynamics of actomyosin-based contractile ring and maintain the cleavage furrow for cell division [7, 8]. In addition to mitotic phase, optimal expression of ADF/cofilin is also critical for G1 to S phase progression. Forced expression of ADF/cofilin can result in G1 phase arrest through destabilization of actin cytoskeleton and upregulation of cell cycle inhibitor p 2 7 k i p 1 [9]. ADF/cofilin is involved in migration, locomotion and metastasis of cancerous cells. It has been
%U http://www.hindawi.com/journals/isrn.cell.biology/2012/597876/