A protein associated with the neurodevelopmental disorder lissencephaly promotes the assembly of dynein–dynactin motor complexes on mRNA cargoes, Dix et al. reveal.
Many mRNAs are transported to specific locations within the cell so that the proteins they encode are synthesized in the right place. In early Drosophila embryos, for example, certain mRNAs are transported to the apical cytoplasm by the minus end–directed microtubule-based motor dynein and its accessory complex dynactin. Dynein and dynactin are recruited to their cargo by adaptor proteins that bind to a “localization signal” in the mRNA. How the assembly and function of the motor complex are regulated is unclear, however.
Dix et al. found that the dynein-associated protein Lis1 was recruited to the localization signals of several Drosophila mRNAs. Fly embryos with reduced levels of Lis1 were defective in transporting these mRNAs to the apical cytoplasm, because their movement toward the minus end of microtubules was impaired. Defects in RNA transport could contribute to the developmental problems associated with lissencephaly, in which the gene encoding Lis1 is mutated.
Dynein transports numerous cellular cargoes, and Lis1 promotes the movement of many, if not most, of them by regulating dynein’s motor activity. This may also be true for the apical transport of mRNAs, but Dix et al. found that Lis1 also promoted dynein’s association with the dynactin complex and the recruitment of these proteins to RNA localization signals. Senior author Simon Bullock now wants to investigate how Lis1 promotes the assembly of the dynein–dynactin complex and to determine whether it remains associated with mRNAs once they start to move.
Text by Ben Short