Distinct functional roles of cytoplasmic dynein defined by the intermediate chain isoforms

Abstract

The motor protein, cytoplasmic dynein is responsible for the movement of a variety of cargoes toward microtubule minus ends in cells. Little is understood about how dynein is regulated to specifically transport its various cargoes. In vertebrates, the dynein motor domain (DYNC1H) is encoded by a single gene; while there are two genes for the five smaller subunits that comprise the cargo binding domain of the dynein complex. The isoforms of the intermediate chain (DYNC1I) provide a good model system with which to study the roles the different isoforms of the cargo domain subunits have in designating specific dynein functions. The intermediate chains (DYNC1I) play a key scaffold role in the dynein complex. In neurons, dynein complexes with different intermediate chain isoforms have distinct roles, including cargo binding and transport. Some of the phospho-isoforms of the intermediate chain also specify binding to specific cargo. These data support the model that cytoplasmic dynein can be specifically regulated through the different isoforms of the subunits.

Keywords: Axonal transport; Cytoplasmic dynein; Cytoskeleton; Intermediate chain phosphorylation; Motor protein.

Figure 1. Domain map of the rat intermediate chain (IC)

The N-terminus is to the left. The coiled-coil is yellow; The two alternative splicing regions are red (A1 & A2); the dimerization domain is blue, the WD repeats are purple. The binding regions of the other dynein subunits and the subunits of dynein regulators, NudE and p150 (dynactin), are show above the map.

Figure 2. Model for Phospho-intermediate Chain Binding to Signaling

A. Dynein binding to the signaling endosomes requires a component in addition to dynactin to detect changes in intermediate chain phosphorylation state (green box). B. Symbol index: NT is neurotrophin; SE is signaling endosome. Modified from Figure 10 in [42].