15 - Cytoplasmic Dynein Function Defined by Subunit Composition

Abstract

Cytoplasmic dynein 1 is a large protein complex composed of six subunits, the motor containing heavy chain (HC) and five smaller subunits (base subunits), which make up the base of the complex. Most of the base subunits have been implicated in cargo binding, and vertebrates have at least two genes for each of these subunits. This chapter discusses the functional roles of the different subunits and evaluates the evidence supporting the hypothesis that differential regulation of cytoplasmic dynein is accomplished by utilizing different isoforms of the five base subunits to create functionally distinct cytoplasmic dynein complexes. Starting with two genes for each subunit and assuming the uniform tissue expression of all the subunit isoforms, and that each subunit only forms homodimers, cells have the potential to generate thirty-two distinct dynein complexes. The study illustrates that distinct dynein functions are correlated with dynein complexes containing different isoforms of the intermediate chain (IC), the light-intermediate chain (LIC), or the DYNLT LC. It also suggests that the LIC and DYNLT isoforms are specific for different cellular “housekeeping” dynein functions, while dynein complexes with different IC isoforms are utilized for neuron-specific functions. However, several important data remain to be established, related to specific dynein functions for the isoforms of the DYNLL or DYNLRB LCs, and the number of potential combinations of dynein base subunits that exist and their functional significance remain to be determined.