17 - Insights into Cytoplasmic Dynein Function and Regulation from Fungal Genetics

Abstract

This chapter deals with the discovery of dynein’s function in the positioning of nuclei and mitotic spindles and genetic studies that link the function of LIS1 and NudE/NudEL to the dynein pathway. It also reviews studies on the functions and regulatory mechanisms of the microtubule plus-end accumulation of cytoplasmic dynein, as well as studies on the biochemical functions of different proteins in the dynein and dynactin complexes. Functional studies of cytoplasmic dynein in the multinucleated filamentous fungi Aspergillus nidulans and Neurospora crassa were initiated by a classic forward genetic approach. The role of dynein in positioning nuclei/spindles has been found in several fungal organisms such as Nectria haematococca, Ustilago maydis, Ashbya gossypii, Aspergillus oryzae, and Candida albicans. Fungal genetics not only made the functional link between individual subunits of the dynein-dynactin complexes and the in vivo function of dynein, but also allowed the identification of several dynein regulators such as LIS1, NudE/NudEL, and mNudC/NudCL that had not been isolated as components of the dynein and dynactin complexes. Fungal model organisms are in general very well suited for detailed biochemical characterization of the proteins involved in dynein function. The accumulation of dynein at the microtubule plus ends is important for the biological functions of dynein in fungi. Thus, the biological role of dynein and its regulation at the plus end will need to be studied in such a context and fungal genetic methods should be of great use in these studies.