The MICAL family at the Rho–Rab interface: coordinating actin dynamics through oxidation and scaffolding

Abstract The actin cytoskeleton is a complex network of proteins that is constantly being remodelled and reorganized to orchestrate numerous essential cellular processes. From the regulation of proliferation, motility, cytokinesis through to signal transduction, and beyond, the dynamic nature of the actin cytoskeleton is vital to the enactment of these cellular functions. As a result, when there are aberrations in cytoskeleton dynamics, adverse consequences may be triggered. For example, dysregulation of the actin cytoskeleton has been linked to several neurodevelopmental and neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. Additionally, actin cytoskeleton dysregulation has been shown to drive cancer growth and invasion, with altered expression levels of actin effectors and regulators being frequently associated with poorer prognoses and more invasive phenotypes. Given the complex and varied roles of the actin cytoskeleton and the ramifications of its dysregulation, the characterization of its key regulators is essential to understand disease etiology and to identify potential new therapeutic targets. This review highlights the interconnections of three protein families that are central to actin cytoskeleton modification, regulation, and function: the MICAL monooxygenase family, and the Rho and Rab GTPase families. The roles of the MICAL protein family and its functions in connecting Rho and Rab protein signalling will be discussed, with a particular focus on MICAL1.