Actin filaments form contractile and protrusive structures that play central roles in many processes such as cell migration, morphogenesis, endocytosis, and cytokinesis. During these processes, the dynamics of the actin filaments are precisely regulated by a large array of actin‐binding proteins. The actin‐depolymerizing factor homology (ADF‐H) domain is a structurally conserved protein motif, which promotes cytoskeletal dynamics by interacting with monomeric and/or filamentous actin, and with the Arp2/3 complex. Despite their structural homology, the five classes of ADF‐H domain proteins display distinct biochemical activities and cellular roles, only parts of which are currently understood. ADF/cofilin promotes disassembly of aged actin filaments, whereas twinfilin inhibits actin filament assembly via sequestering actin monomers and interacting with filament barbed ends. GMF does not interact with actin, but instead binds Arp2/3 complex and promotes dissociation of Arp2/3‐mediated filament branches. Abp1 and drebrin are multidomain proteins that interact with actin filaments and regulate the activities of other proteins during various actin‐dependent processes. The exact function of coactosin is currently incompletely understood. In this review article, we discuss the biochemical functions, cellular roles, and regulation of the five groups of ADF‐H domain proteins. © 2011 Wiley‐Liss, Inc.

Background and Purpose-Exposure of animals for a few hours to moderate hypoxia confers relative protection against subsequent ischemic brain damage. This phenomenon, known as hypoxic preconditioning, depends on new RNA and protein synthesis, but its molecular mechanisms are poorly understood. Increased expression of IL-6 is evident, particularly in the lungs of animals subjected to hypoxic preconditioning. Stanniocalcin-1 (STC-1) is a 56-kDa homodimeric glycoprotein originally discovered in bony fish, where it regulates calcium/phosphate homeostasis and protects against toxic hypercalcemia. We originally reported expression of mammalian STC-1 in brain neurons and showed that STC-1 guards neurons against hypercalcemic and hypoxic damage. Methods-We treated neural Paju cells with IL-6 and measured the induction of STC-1 mRNA. In addition, we quantified the effect of hypoxic preconditioning on Stc-1 mRNA levels in brains of wild-type and IL-6 deficient mice. Furthermore, we monitored the Stc-1 response in brains of wild-type and transgenic mice, overexpressing IL-6 in the astroglia, before and after induced brain injury. Results-Hypoxic preconditioning induced an upregulated expression of Stc-1 in brains of wild-type but not of IL-6 -deficient mice. Induced brain injury elicited a stronger STC-1 response in brains of transgenic mice, with targeted astroglial IL-6 expression, than in brains of wild-type mice. Moreover, IL-6 induced STC-1 expression via MAPK signaling in neural Paju cells. Conclusion-These findings indicate that IL-6 -mediated expression of STC-1 is one molecular mechanism of hypoxic preconditioning-induced tolerance to brain ischemia.

Animals exposed for a few hours to low oxygen content (8%) develop resistance against further ischemic myocardial damage. The molecular mechanism(s) behind this phenomenon, known as hypoxic preconditioning (HOPC), is still incompletely understood. Stanniocalcin-1 (STC-1) is an evolutionarily conserved glycoprotein originally discovered in fish, in which it regulates calcium/phosphate homeostasis and protects against toxic hypercalcemia. Our group originally reported expression of mammalian STC-1 in brain neurons and showed that STC-1 is a prosurvival factor that guards neurons against hypercalcemic and hypoxic damage. This study investigates the involvement of STC-1 in HOPC-induced cardioprotection. Wild-type mice and IL-6-deficient (Il-6(-/-)) mice were kept in hypoxic conditions (8% O(2)) for 6 h. Myocardial Stc-1 mRNA expression was quantified during hypoxia and after recovery. HOPC triggered a biphasic upregulation of Stc-1 expression in hearts of wild-type mice but not in those of Il-6(-/-) mice. Treatment of cardiomyocyte cells in culture with hypoxia or IL-6 elicited an Stc-1 response, and ectopically expressed STC-1 in HL-1 cells localized to the mitochondria. Our findings indicate that IL-6-induced expression of STC-1 is one molecular mechanism behind the ischemic tolerance generated by HOPC in the heart.