Lysosomal enzyme processing and trafficking in the social amoeba Dictyostelium discoideum

Dictyostelium discoideum is a single-celled protist that undergoes multicellular development in response to nutrient deprivation. For close to a century, D. discoideum has been used as a model system for studying conserved cellular and developmental processes such as chemotaxis, cell adhesion, and cell differentiation. In the later decades of the 20th century, intensive research efforts examined the synthesis, trafficking, and activity of lysosomal enzymes in D. discoideum. Subsequent work revealed that lysosomes are essential for all stages of the D. discoideum life cycle and the genome encodes dozens of homologs of human lysosomal enzymes, including those associated with lysosomal storage diseases. Additionally, protocols for examining the trafficking and activity of lysosomal enzymes in D. discoideum are well-established. Here, we provide a comprehensive up-to-date review that summarizes our current knowledge of lysosomal enzyme processing and trafficking in D. discoideum, with an eye towards re-establishing D. discoideum as a model eukaryote for studying the functions of conserved lysosomal enzymes and the pathways that regulate their trafficking.