Cell Motility: From Molecules to Organisms (Life Sciences)
The study of cell motility encompasses a wide range of approaches andtechniques. This book provides a series of reviews by experts on different aspects of cell motility, from those studying molecules in vitro to those studying whole organisms. The reviews were commissioned from speakers at the 5th Abercrombie Symposium on Cell Motility, held in Oxford, UK in September 2003. These symposia are held every five years to commemorate the work of Michael Abercrombie, who was one of the pioneers in studying cell behaviour. Many of the concepts on how cells move that we now take for granted were established through his careful analysis. He made numerous timelapse films of moving cells cultured in vitro, and established that they extended lamellipodia and that when they met each other normal cells stopped moving (contact inhibition), rather than crawling over each other. The Abercrombie Symposia have become a forum for presenting the latest results in Cell Motility research.
Several articles in this volume report the enormous progress that has been made in the last few years in establishing at a molecular level how cells extend lamellipodia. The biochemical basis for the actions of actin-regulatory proteins such as the Arp2/3 complex, cofilin, profilin and capping proteins has been intensively investigated, and is discussed by Tom Pollard. A major discovery of the last five years is that the WASp-related proteins are central players in signal transduction from the plasma membrane to the Arp2/3 complex, and the regulation and action of WASp proteins is the topic of articles by the groups of Laura Machesky, Robert Insall and Tadaomi Takenawa.
Severing of actin filaments as well as de novo nucleation is important for altering cell morphology, as described in the chapters by Daniel Louvard and John Condeelis. A new player in the actin dynamics field is dynamin, a GTPase first characterized for its role in vesicle fission; the involvement of dynamin in cell motility is introduced by Orth and colleagues.
Lamellipodium extension is required for cell migration, but the cell body needs to move to follow the extension. Several events are critical for this. First, cell adhesion to its surroundings is important for the cell to exert a traction force. Meg Titus discusses the contribution of talin, which binds to transmembrane integrin receptors, and myosins with sequence homology to talin, in cell adhesion. Second, loss of cell adhesion by cell detachment selectively at the rear of the cell is essential for productive locomotion; Anna Huttenlocher reviews the role of the protease calpain in this process. Third, actin interaction with myosin is important for generating contractile forces and movement of actin filaments inside cells, and Soldati and Kistler discuss how class I myosins contribute to these processes.
Following the movement of and interaction between proteins within living cells is essential for understanding how they contribute to cell motility. Mark Holt and colleagues describe different microscopy techniques for tracing molecules in living cells. Delivery of new membrane components to the plasma membrane is often essential for initiating and/or maintaining membrane protrusion, for example during cell migration and phagocytosis. Pierre Chavier’s group describe how the small GTPase ARF6 contributes to this process.
As well as the actin cytoskeleton, microtubules play a crucial role in cell migration in many cell types. This has been known for many years, but it is only recently that the molecular basis for the contribution and regulation of microtubules has been revealed. The Rho GTPases that are well known to regulate actin polymerization turn out to be central to microtubule dynamics as well, as reviewed here by Wittmann and Waterman-Storer. Recently it has become clear that microtubules are important for regulating the turnover of integrin-mediated adhesions to the substratum, as illustrated in the review by Alexander Bershadsky and colleagues.
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