Cell motility is a fundamental cellular process required for embryogenesis, tissue development, cancer metastasis/invasion, neuron network formation and wound healing. The actin cytoskeleton, one of pivotal molecular bases for cell motility, is regulated by various processes such as nucleation, polymerization, stabilization, bundling, branching, severing, capping and so on. Recent studies have progressively revealed the molecular mechanisms of actin dynamics mediated by a variety of actin-binding proteins and the involvement of them in cell motility. In this special issue, we focus on several actin-binding proteins involved in cell motility, migration and adhesion.
Dr. Mak highlights that p53, the most famous tumor suppressor, regulates cell invasion and migration via regulation of invadopodium/podosome. p53 is not an actin-binding protein in itself, but it plays an important role in the regulation of invadopodium/podosome formation, that are dynamic actin-based structures and act as sites of cell adhesion and ECM remodeling.
Caldesmon is an actin-linked regulatory protein, which binds and stabilizes actin filaments, as well as regulating actin-myosin interaction. Dr. Mayanagi and I review the roles of caldesmon in diversified cell processes such as cell migration, invasion, cell cycle progression and secretion as well as regulation of contraction.
Filamin is one of major F-actin cross-linking protein and is involved in a lot of various cellular processes. Dr. Nakamura and colleagues review the molecular features of filamin and highlight interactions with its numerous binding partners.
A lot of actin-linked proteins are controlled by the downstream effectors of Rho-family small GTPases. Dr. Spiering and Dr. Hodgson review current knowledge of Rho GTPases-dependent regulation of the actin cytoskeleton and cell motility. They also introduce current approaches to study the spatio-temporal regulation of Rho GTPases and rearrangement of the actin cytoskeleton in living cells using state-of-the-art methods.
Dr. O'Neill and colleagues overview the molecular function of tropomyosins, which are broadly expressed actin-binding protein family. They also focus on the recent topics of isoform-specific roles of tropomyoin in cell migration and invasion.
The dynamic regulation of branched actin is important for cellular processes including membrane protrusion formation and membrane trafficking. Dr. Kirkbride and colleagues overview the molecular features of cortactin, a key regulator of branched actin, and the role in cell migration and invasion via regulation of the actin-based protrusive structures such as lemellipodia and invadopodia/podosomes.
The linking mechanism between plasma membrane and the actin cytoskeleton is necessary for membrane protrusion, cell-cell and cell-matrix adhesion as well as organization of cell morphology. ERM (Ezrin, Radixin and Moesin) proteins function as linkers between the membrane and the underlying actin cytoskeleton, and also provide a platform for the numerous signaling proteins. Dr. Arpin and colleagues review the functions and the regulatory mechanisms of ERM family proteins, in particular with the focus on epithelial cell adhesion and migration.
This series of reviews promotes interest in a diverse field of biological science and hopefully provides a cornerstone for basic and clinical approaches.
About Dr. Kenji Sobue
Dr. Kenji Sobue is Chairman of the Department of Neuroscience at the Osaka University, Graduate School of Medicine. He is currently moving to Iwate Medical University, as Vice President. Dr. Sobue received his M.D. in 1973 at the Iwate Medical University and Ph.D. in 1977 at the Osaka University, Graduate School of Medicine. He is known his work in the field of the actin cytoskeleton, having discovered caldesmon and revealed the regulation mechanism of the actin cytoskeleton. He expanded his interest in neuroscience, having isolated postsynaptic scaffolding proteins involved in actin-linked synaptic dynamics. He has currently focused on neuronal migration, synaptic dynamics and neuronal network formation involved in the actin cytoskeleton and their abnormalities in psychiatric disorders.