Dynamic rearrangement of actin filament networks is critical for cell motility, phagocytosis, and endocytosis. Coronins facilitate these processes, in part, by their ability to bind F-actin. We previously identified a conserved surface-exposed arginine (R30) in the b-propeller of Coronin 1B required for F-actin binding in vitro and in vivo. However, whether this finding translates to other coronins has not been well defined. Using quantitative actin binding assays, we show that mutating the equivalent residue abolishes F-actin binding in Coronin 1A but not Coronin 1C. By mutagenesis and biochemical competition, we have identified a second actin binding site in the unique region of Coronin 1C. Interestingly, leading edge localization of Coronin 1C in fibroblasts requires the conserved site in the β-propeller but not the site in the unique region. Furthermore, in contrast to Coronin 1A and Coronin 1B, Coronin 1C displays highly cooperative binding to actin filaments. Here, we highlight a novel mode of coronin regulation, which has implications for how coronins orchestrate cytoskeletal dynamics.
Epigenetic silencing of gene expression is important in cancer. Aberrant DNA CpG island hypermethylation and histone modifications are involved in the aberrant silencing of tumour-suppressor genes. LSD1 (lysine-specific demethylase 1) is a H3K4 (histone H3 Lys4) demethylase associated with ... more
Distinct spatiotemporal Ca2+ signalling events regulate fundamental aspects of eukaryotic cell physiology. Complex Ca2+ signals can be driven by release of Ca2+ from intracellular organelles that sequester Ca2+ such as the ER (endoplasmic reticulum) or through the opening of Ca2+-permeable ... more
Genetically modified mice mimicking ODDD (oculodentodigital dysplasia), a disease characterized by reduced Cx43 (connexin 43)-mediated gap junctional intercellular communication, represent an in vivo model to assess the role of Cx43 in mammary gland development and function. We previously ... more