A molecular genetic analysis of the interaction between the cytoplasmic dynein intermediate chain and the Glued (dynactin) complex

The microtubule motor cytoplasmic dynein performs multiple cellular functio ns; however, the regulation and targeting of the motor to different cargoes is not well understood. A biochemical interaction between the dynein inter mediate chain subunit and the p150-Glued component of the dynein regulatory complex, dynactin, has supported the hypothesis that the intermediate chai n is a key modulator of dynein attachment to cellular cargoes. In this repo rt, we identify multiple intermediate chain polypeptides that cosediment wi th the 19S dynein complex and two differentially expressed transcripts deri ved from the single cytoplasmic dynein intermediate chain (Cdic) gene that differ in the 3' untranslated region sequence. These results support previo us observations of multiple Cdic gene products that may contribute to the s pecialization of dynein function. Most significantly, we provide genetic ev idence that the interaction between the dynein intermediate chain and p150- Glued is functionally relevant. We use a genomic Cdic transgene to show tha t extra copies of the dynein intermediate chain gene act to suppress the ro ugh eye phenotype of the mutant Glued(1), a mutation in the p150-Glued subu nit of dynactin. Furthermore, we show that the interaction between the dyne in intermediate chain and p150-Glued is dependent on the dosage of the Cdic gene. This result suggests that the dynein intermediate chain may be a lim iting component in the assembly of the dynein complex and that the regulati on of the interaction between the dynein intermediate chain and dynactin is critical for dynein function.