Cell Motility Moves Ahead

Cell Motility: From Molecules to Organisms Anne Ridley, Michelle Peckham, and Peter Clark, Eds.Chicester, United Kingdom: John Wiley & Sons (2004) 384 pp., $180.00Cell motility has fascinated scientists for decades. The earliest studies of tissue culture cells using time-lapse cinematography by Michael Abercrombie and coworkers in the 1950's showed cell behaviors that we are still struggling to understand today (see Abercrombie and Heaysman [1954], Nature 174, 697). This pioneering work is celebrated every five years with a symposium on cell motility, held most recently in September of 2002 at Oxford, UK. Growing from this meeting is a volume of review articles on cell motility (Cell Motility: From Molecules to Organisms) that will be the main subject of this resource review.This volume shows the tremendous progress that the field has made in the last decade and reads a bit like a “state of the field” address to the cell biology community. Unlike its counterpart in American presidential politics, this address is (mostly) free of partisan attacks and tedious rhetoric. Twenty solid reviews cover advances in a number of areas, and the editors have done a nice job of picking first-rate authors in their respective areas of expertise. The order of the reviews within the volume, however, lacks organization and seems rather random. That minor criticism aside, this is an excellent set of reviews that is well worth a look. It will likely prove most valuable to those just entering the field or for people who want to catch up with the latest findings in motility.Cell motility has a number of classical themes that are well represented in this book. Many of these areas have been studied since the beginnings of the field and include actin dynamics, cell adhesion, chemotaxis, myosin motor function, and membrane dynamics. In addition to these areas, new themes have emerged in the field such as the connection(s) between the microtubule cytoskeleton and adhesive structures and actin dynamics. Furthermore, the motility of cell types beyond fibroblasts and amoebae is being examined with increasing intensity. Cell motility, like all areas of science, has always been limited by experimental methodology. New methods and imaging techniques are expanding our understanding of motility mechanisms inside of living cells. Finally and perhaps most exciting are new methods for studying cell motility in vivo.Dynamic reorganization of the cytoskeleton provides the driving force for cell motility, and this topic is ably covered by a number of reviews in this book. Pollard starts things off with an overview of the current understanding of actin dynamics at the leading edge of motile cells. While this topic has been extensively covered by reviews in the last few years, this article distills a large number of experiments into a clear conceptual framework that is invaluable for the field. Reviews from the Machesky, Takenawa, and Insall groups delve into the details of Arp2/3 activation via the WASp/SCAR family of proteins. This pathway is perhaps the best-characterized example of signaling from cell surface receptors to actin reorganization and has been the target of intense effort by many groups over the last few years. Other proteins that control actin dynamics, with the exception of Villin, are largely ignored in this volume. Some of the most exciting work in this area is connecting the Formin family of proteins to novel steps in actin assembly such as anti-capping. Since much of this work is so recent, it was probably not possible to include because of publishing schedules. The contribution of microtubules to cell motility is covered by reviews from the Bershadsky and Waterman-Storer groups. In light of the explosion of new studies connecting the actin and microtubule cytoskeletons, this area will likely require a whole new set of reviews the next time the Abercrombie Symposium is held.Adhesion of cells to their underlying substrate and to other cells is a critical step in cell motility and has been studied since the earliest days of motility research. Cell-substratum adhesion occurs mainly through integrins that are clustered in specialized regions of the plasma membrane called focal adhesions. Reviews from the Bershadsky and Horwitz groups discuss the formation and dynamics of focal adhesions, while a review from Huttenlocher describes how to tear them apart using the protease Calpain. Cell-cell adhesion is covered by an interesting review from the Nelson group. This review discusses the interplay between the Rho-type GTPase signaling and E-Cadherin-based cell-cell adhesion in epithelial cells.Chemotaxis is one of the most fascinating problems in all of cell motility, but also one of the most resistant to a complete molecular solution despite decades of experiments. To understand chemotaxis, one first must have a grasp of the basic machinery of cell movement and then understand how signal transduction pathways modulate this basic machinery. On top of that, one must understand how a cell establishes and then maintains polarity. Since these separate problems are quite daunting individually, it is amazing that we understand as much as we do about chemotaxis. Two reviews cover current aspects of chemotaxis: the Condeelis group covers growth factor-mediated chemotaxis in mammary carcinoma cells and the Firtel group covers G protein-coupled receptor chemotaxis in Dictyostelium. It is interesting to compare and contrast how these different signaling pathways in very different cell types end up producing the same basic end result.One of the early realizations of cell motility research was that nonmuscle cells, like muscle fibers, also contained significant amounts of actin and myosin. With the advent of molecular cloning, a flood of so-called “unconventional myosins” was released. These proteins participate in many cellular processes including cell motility. While their role in motility in mammalian systems is just being established, many of these myosins have been well studied in Dictyostelium. This volume contains reviews on unconventional myosins from the Titus and Soldati groups. Titus covers the role that myosin VII plays in cell adhesion and phagocytosis, while the review from Soldati's group covers the role that type I myosins play in actin dynamics. Myosin motors are a huge family of proteins and will likely continue to supply surprises for years to come.Membrane dynamics is another key factor in cell motility. Cells have to dynamically control the trafficking of membrane proteins and vesicle contents to and from the plasma membrane. This process has an impact on many aspects of cell motility including the recycling of adhesion receptors, adaptation of signaling pathways, and alterations in the biophysical properties of the plasma membrane itself. A review from the McNiven group covers the role of dynamin—a key protein in regulating membrane dynamics. This review does an excellent job of concisely summarizing a large body of work on dynamin and posing some intriguing questions for future studies. The Chavrier group covers another GTPase involved in membrane trafficking—ARF6. Elucidating the subtle interplay between membrane dynamics and cell movement will require many creative and thoughtful future studies.In addition to the classical themes of cell motility, this volume also touches on some interesting new areas in the field. The motility of cell types such as neurons is being studied with increasing intensity. The Nobes group has an interesting review on the repulsion of neuronal growth cones by Eph receptors. Other reviews from the Birchmeier, Keller, and Horwitz groups deal with the migration of cells in vivo during development. Studying cell motility in these more complicated 3D environments is much more difficult than in tissue culture but clearly represents an important future direction of the field. Finally, the Dunn group offers a very nice overview of several new imaging techniques that are already having a large impact on motility research. This volume of reviews shows what an exciting a time this is for cell motility and how much there is still left to explore.