The question of how cells organize their interiors is a central theme in cell biology. While a great deal is known about how proteins are sorted to various membrane-bound compartments within the cell, very little is known about how proteins are sorted to particular domains within the cytoplasm. One mechanism that cells use to accomplish this task is to sort information in the form of messenger RNA (mRNA) to particular regions of the cell. This sorting process ensures that the proteins encoded by localized messages are restricted to discrete domains by virtue of the fact that they are only synthesized at those sites where the instructions to make them, the mRNAs, are found. It has long been suspected that the transport of mRNAs within the cytoplasm is accomplished by motors that move along microtubules, which are tiny filaments within the cell. However, the identity of the motors and the complexes that recruit them to particular mRNAs has remained elusive.

One of the best-characterized examples of mRNA localization is in Drosophila oogenesis where the localization of the oskar and bicoid messages is responsible for establishing the anterior-posterior axis of the embryo. The localization of oskar and bicoid mRNAs presents an interesting problem for the study of mRNA transport since these mRNAs are differentially sorted with oskar mRNA being sent to the posterior pole of the oocyte, while bicoid mRNA remains at the anterior. The molecular basis for this sorting event is completely unknown.

The Wilhelm lab is interested in identifying the machinery responsible for mRNA localization using the transport of oskar and bicoid mRNAs as a model system. As part of this work, Wilhelm has isolated a complex of seven proteins that are associated with Exuperantia (Exu), a protein genetically implicated in bicoid mRNA transport to the anterior of the Drosophila oocyte. Surprisingly, this complex contains the posteriorly localized mRNA, oskar, and mutations in exu disrupt oskar mRNA localization. These results suggest that this complex may play a role in both the anterior and posterior localization pathways.

A number of proteins in the Exu complex are expressed outside of the ovary. Wilhelm believes that these proteins might be part of a core-transport complex that is used to localize mRNAs in many different cell types. To test this, the lab’s researchers developed a new genome-wide screening method for identifying new localized mRNAs. This technique should allow the identification of new localized messages in the ovary as well as in other tissues. The identification of localized messages in other tissues, such as the central nervous system, will allow the Wilhelm lab to test if the components of the Exu complex play a role in mRNA localization events outside of the ovary.