16 - Insights into cytoplasmic dynein function and regulation from fungal genetics

Abstract

Studies in fungal model organisms have contributed significantly to our knowledge of dynein function and regulation. Fungal molecular genetic studies first uncovered the function of cytoplasmic dynein in the positioning of nuclei/spindles. Fungal genetics led the way toward identification of several important regulators in the dynein pathway, including LIS1, the product of a causal gene for lissencephaly, a human brain developmental disorder. Live cell imaging studies provided insights into the mechanisms of microtubule plus-end accumulation of cytoplasmic dynein and how plus-end dynein is functionally involved in spindle positioning and transport of early endosomes. Furthermore, fungal genetic studies contributed to our knowledge of how dynein physically interacts with early endosomes in vivo and how other cargos hitchhike on early endosomes for intracellular positioning. These studies have opened up new avenues of investigations that will lead to a better understanding of dynein-mediated organelle positioning in eukaryotic cells.