Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila gene Glued

CYTOPLASMIC dynein is a microtubule-activated ATPase which produces force towards the minus ends of microtubules^1,2. It is thought to be responsible for retrograde axonal transport and other aspects of organelle motility^2-6 and may have a role in the poleward movement of mitotic chromosomes^7,8. Cytoplasmic dynein is an oligomeric complex of two catalytic heavy chains and a number of accessory subunits^1,9,10. We now report the cloning and sequencing of a complementary DNA for one of these species, a cytoplasmic dynein-associated polypeptide of relative molecular mass 150,000 (M_r 150K). A full-length cDNA was found to contain an open reading frame of 4.0 kilobases, which is predicted to encode a polypeptide of M_r 145K¹¹. It has extensive homology with the product of the Drosophila gene Glued, which encodes a poly-peptide of M_r 148K¹¹. The Glued mutation is dominant, with pleiotropic developmental defects in heterozygotes and an em-bryonic lethal phenotype in homozygotes. As dominant mutations may involve disruption of normal protein-protein interactions, the Glued mutation should provide insight into the mode of action of cytoplasmic dynein in vivo.