Regulators of the cytoplasmic dynein motor

Abstract

Cytoplasmic dynein is the only microtubule minus end-directed motor in the cytoplasm of most eukaryotic cells and therefore carries out a huge range of functions, including organelle and mRNA transport, nuclear and spindle positioning, and transport of the mitotic spindle assembly checkpoint proteins. The dynein motor functions as a holoenzyme, assembling into a complex with several smaller, non-catalytic subunits that help to connect it with dynein cargos as well as other regulatory factors that help to couple the dynein motor to its many cellular functions. Two dynein adaptors, dynactin and a complex of lissencephaly 1 (Lis1) and nuclear distribution protein E (NUDE) or NUDE-like (NUDEL) seem to be ubiquitously required for all dynein functions. Dynactin increases dynein processivity in vitro and helps to link dynein with its cargos and anchor points in the cell. LIS1–NUDE and LIS1–NUDEL might act primarily as a switch for dynein activity. Both dynactin and LIS1–NUDE and LIS1–NUDELmodulate dynein association with the plus ends of microtubules, which seems to be important for the delivery of dynein to its sites of activity. Bicaudal D and the Rod–ZW10–Zwilch (RZZ) complex are multifunctional dynein adaptors, but are restricted to metazoan organisms. Bicaudal D links dynein with several interphase cargos, and RZZ, with its partner Spindly, docks dynein at the mitotic kinetochore and might help to regulate the transition between the several dynein functions at the kinetochore. Small GTPases, which are highly specific to subcellular compartments, regulate dynein association with some of its cargos. Dynein's adaptors are heavily interconnected by physical interaction and by phenotype and so must cooperate to coordinate dynein function in the cell.