Current Tools and Methodologies to Study Non-muscle Myosins

TOPICAL COLLECTIONS

Guest Editor

Natali Fili

University of Lincoln, School of Life Sciences, UK

Dr. Natali Fili is a Lecturer in Biomedical Biochemistry at the School of Life Sciences, at the University of Lincoln. Her research is focused on the regulation and function of the unconventional myosin, myosin VI, using quantitative cell biology. Dr. Fili completed her PhD in Cell Biology, at CRUK-London Research Institute. She then pursued a Postdoctoral Fellowship at the MRC-National Institute for Medical Research (NIMR), London, developing single-molecule methods for DNA helicases. She then moved to the Ludwig Maximilian University (LMU) of Munich, Germany, where she first investigated unconventional myosins. Following a career break, she joined the School of Biosciences, at the University of Kent, as a Royal Society Newton International Fellow and then as Postdoctoral Research Associate in the group of Dr. C. Toseland. There, she expanded her studies on unconventional myosins, to reveal the regulation mechanism of myosin VI and to uncover its fundamental role in the spatial organisation of transcription. She then relocated with the group of Dr. Toseland to the Department of Oncology and Metabolism, at the University of Sheffield.

Collection Overview

Myosins are actin-based motor proteins that harness energy from ATP hydrolysis to generate mechanical work. In eukaryotes, the myosin superfamily consists of 35 classes of motors, which are further divided into two groups: the conventional class II myosins and the unconventional myosins. In addition to its role in muscle contraction, the non-muscle myosin II (NMII) is a key regulator of cellular morphology. By assembling with actin into bipolar filaments, called stress fibers, NMII plays a key role in cell motility, adhesion, and cytokinesis. Unconventional myosins, the largest group in the family, serve a plethora of vital cellular processes, ranging from intracellular transport and signal transduction, to gene expression. This multi-functionality is achieved through the ability of these myosins acting as cargo transporters, membrane remodelers, tension sensors, and/or molecular anchors. This relies on a tightly regulated interaction with the actin cytoskeleton, cellular membranes, and a broad range of protein adaptors.

Given the involvement of non-muscle myosins in vital cellular processes, it is not surprising that disruption of their functionality has been associated with various pathologies, ranging from hearing loss and vascular diseases, to neurological disorders and cancer. In order to dissect the mechanistic details of their regulation and function and, therefore, their role in disease, we need to follow a holistic, interdisciplinary approach. During the past decade, the toolkit available for the study of these myosins has been greatly enriched with methodologies that enable high temporal and spatial resolution, and allow manipulation of myosins’ intracellular functions. Currently, the methodologies available include kinetic measurements, structural biology techniques, optogenetic strategies, super-resolution microscopy, and in vitro and live cell single molecule imaging. This Methods Collection aims to bring together, in a video-based format, traditional and newly emerged biophysical methodologies, which have been adapted for the study of non-muscle myosins.