Arginine Kinase Expression and Localization in Growth Cone Migration

Abstract

Migrating neuronal growth cones exert traction forces that are generated by ATP-driven F-actin/myosin interactions. Sustained generation of these forces may require an energy supply mediated by the guanidino kinases, creatine kinase and arginine kinase. We cloned and sequenced grasshopper arginine kinase and examined its expression during embryogenesis and its subcellular localization in vivo and in vitro. During the first half of embryogenesis, arginine kinase is expressed selectively in a small percentage of ectodermal cells (dorsal closure cells), in a small percentage of mesodermal cells (muscle pioneers), and throughout the developing CNS. Most of these cell types are motile, including nascent neurons, muscle pioneers, dorsal closure cells, and many CNS glia. Neuroblasts also strongly express arginine kinase; they are nonmotile but are undergoing repeated rounds of (ATP-dependent) mitosis. Arginine kinase is colocalized with F-actin in a narrow band along the leading edges of lamellipodia of migrating glia. In neurons undergoing axonogenesis, arginine kinase is concentrated in growth cones and extends to the tips of filopodia. The amount of arginine kinase varies widely between growth cones, even between different growth cones of the same neuron. Energy for growth cone migration appears to be mobilized by (1) selective expression of arginine kinase by neurons, (2) localization of arginine kinase within growth cones, and (3) concentration of arginine kinase within specific growth cones, depending on the traction forces being generated. Mobilization of guanidino kinases may participate in the selective growth of specific growth cones.