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The actin cytoskeleton has been studied for more than fifty years now. Ample studies have documented its fundamental role in cell motility and migration and, especially in the last two decades, tremendous progress has been made to understand the biochemistry of this complex system in relation to its cellular function. The actin system is a multipurpose machine for the cell and is essential for virtually all cellular processes. The actin cytoskeleton is an architectural element, it generates the force for cell migration and for muscle contraction, it is involved in endocytosis, and filaments serve as tracks for sorting cellular components. In the various chapters of this book the role of the actin cytoskeleton in these very different cellular processes is described. As a consequence of its multitasking function, abnormalities in this essential structural component frequently result in disease. Mutations and deregulation of cytoskeletal proteins cause a wide variety of disorders, including muscle and cardiac myopathies, neuronadegenerative diseases and cancer. The first three chapters deal with various molecular properties of components of the actin cytoskeleton in relation to cellular function (and dysfunction). In Chapter 1 Vandamme and coworkers discuss the major building block of the actin cytoskeleton, the actin molecule itself. The paper focuses on gene structures and the tissue and developmental regulation of the six mammalian actin isoforms. Mutations in the actin molecule leading to diseases are discussed as are pathophysiological situations connected to particular actin isoforms. In Chapter 2 the group of Prof. Hüttelmaier gives an overview of an emerging field in actin cytoskeleton research; that of subcellular sorting of the cytoplasmic actin isoforms and its role in establishing polarity via posttranscriptional control of gene expression. Intriguing is the dual property of actin in this, it functions as a track and anchoring scaffold for its own synthesis. In a next chapter by Veniere et al. the biochemistry of actin and actin binding proteins is summarized and put into a context of the formation of subcellular structures, lamellipodia, filopodia and stress fibers, typically associated with cell migration. In the last decade, the actin cytoskeleton also gained clinical importance with the growing awareness of its crucial role during deregulated tumor cell invasion. Therefore two chapters are entirely devoted to the actin cytoskeleton in cancer cell migration. In Chapter 4 Prof. Roy and his team describe the deregulations in the actin system leading to tumor cell migration, expanding on the regulation by Rho-GTPases and polyphosphoinositides. In Chapter 5, Debeir and colleagues outline the rationales for using particular tools to study cell migration assays and discusses, in-depth, global and single cell assays, microscopy and image acquisition technologies, and software tools to study the migratory behavior of cancer cells in in vitro and in vivo model systems. The next four chapters focus on specialized systems. In Chapter 6 Prof. Dent updates on progress made on the role of the actin cytoskeleton in the differentiation of neurons including neuronal migration through axon outgrowth and guidance to synaptogenesis. In Chapter 7, Dr. Sonnemann and Prof. Ervasti, revisit some actin isoforms for their role in muscle development and formation of substructures that are typical for muscle cells and also describe actin diseases in skeletal and cardiac muscle. Dr. Hinz describes, in Chapter 8, the intricate relation between the (maturing) adhesion machinery and the actin cytoskeleton, its role in mechanosensing and in transmitting mechanical stress signals. An equally complex interplay exists between the actin cytoskeleton and the plasma membrane. Prof. Qualmann and coworkers discuss this in the final chapter giving an extensive overview of multidisciplinary research that has advanced our understanding on the cellular pathways and coordinated events leading to formation of vesicles, in which the actin cytoskeleton is instrumental. We acknowledge all authors for their expert contributions. No book of this size on the actin cytoskeleton can be complete, but with this book we have covered a large part of the current research directions in this field. As is evident from the concluding remarks in each of the chapters our work for understanding the role of the actin cytoskeleton is far from complete. Despite many years of intensive and elegant research, many intriguing questions remain but we hope by publishing this book we incite (young) scientists to take up research in the wonderful world of the actin cytoskeleton.