Cell locomotion and chemotaxis

Biology Department, University of Pennsylvania, Philadelphia, Pennsylvania, USA Current Opinion in Cell Biology 1989, 1:80-86 Introduction Locomotion of a cell involves a number of interdepen- dent processes, including force generation for movement of the cell mass from one site to another, protmslon of cellular processes in the direction of movement, retrac- tion of posterior processes, and formation and breakage of adhesive contacts between the cell and the substrate. During locomotion, these processes must be coordinated and repeated either periodically or continuously. Since neither membranous nor cytoplasmic components are synthesized fast enough for the locomotion processes, the cellular components must be recycled. Finally, since both the rate and direction of locomotion can be mod- ulated by chemoattractants, some factors must regulate these processes. Some recent exciting advances in our understanding of these processes are reported here. Generation of force In all recent models of cell locomotion, myosin plays an essential role in creating the force that moves the cell mass. Contractions of actomyosin along the axis of the cell might pull cytoplasm forward. Also, contractions of cortical actomyosin in the rear might push cytoplasm for- ward and create an intracellular pressure necessary for pseudopod extension. It was therefore astonishing to learn from two recent papers [1,2] that Dicfyostelium discoideum amoeba (DDA) exhibit cell locomotion and chemotaxis when the heavy chain of myosin had been essentially eliminated. Myosin synthesis was suppressed either by transformation with an antisense RNA or by recombination of the gene for the heavy chain of myo- sin with a truncated version containing only the heavy meromyosin portion. The transformed cells extend pseu- dopods, translocate and even exhibit chemotaxis. How- ever, they move slowly and show less polarity (persis- tence in direction of movement) than control cells. That a cell can translocate in the absence of a 'muscle° like' myosin has refocused attention on 'small myosins'. These myosins, identified in Acanthamoeba and DDA where they are called 'myosin I', have a molecular weight of about 100 kD and exist only as monomers, unable to form filaments. Acanthamoeba has two forms, myosin 1A and lB. Each has an actin-activated ATPase and a second actin binding site enabling them to cross-link actin fila- ments. Beads coated with these small myosins (as well as the HMM fragment of muscle myosin) move along actin filaments in the presence of ATP [3,4] (Hynes et al., Cell 1987, 48:953-963). A vertebrate protein, the 110 kD protein of intestinal mi- crovilli, resembles these small myosins (Collins and Bo- rysenko, J Biol Chem 1984, 259:14128-14135). The pro- tein binds actin in an ATP-sensitive manner and decorates actin filaments with the familiar arrowhead pattern typical of muscle myosin fragments [5,6]. The ionic dependence of its ATPase activity parallels that of muscle myosin and the Mg 2+-ATPase activity can be slightly stimulated by actin [7,8]. If future studies show that DDA require small myosins for locomotion, it will be exciting to search for these molecules in other vertebrate cells. Protrusion The protrusions at the front of a locomoting cell are filled with filamentous actin. Various agents that induce protru- sions shift the polymerization state of actin from globu- lar (G) to filamentous (F) actin [9]. Apparently, the actin polymerizes at the tip of the protrusion and then the actin filament moves back [10,11]. Blocking actin polymeriza- tion with cytochalasin inhibits the formation of the pro- tmsion [12]. An important issue, then, is how the cell regulates the level and location of actin polymerization. The intracellular concentration of G-actin ( ~ 100 pmol/1) is well above the critical concentration for actin poly- merization in vitro (~ 0.1 pmol/1). Cytoplasmic proteins could prevent polymerization by binding to G-actin. One such protein, profilin, binds G-actin with a K D of 1-10 {unol/1. In platelets, there appears to be only about 0.2 mol profilin/mol actin (determined by its binding to Abbreviations ADF--actin depolymerization factor; ATP--adenosine triphosphate; DDA--Dictyostelium discoideum amoeba; EGF~epidermal growth factor; F-actin filamentous actin; G-actin~lobular actin; Gi--protein of the i subtype; ltMM--heavy meromyosin; IRM~intefference reflection microscopy; mRNA--messenger RNA; PIP--phosphatidylinositolphosphate; PIP2--phosphatidylinositolbisphosphate; PMN--polymorphonuclear leukocytes; PI-phospholipase~phsopbatidylinositol phospholipase; 3T3 cells~a mouse fibroblast cell line. 80 (~) Current Science Ltd ISSN 0955-0674