Insights into mRNA transport in neurons

Many large or morphologically complex cells compartmentalize information by targeting either mRNAs or proteins to specific domains and maintain the localization of these molecules over time. These distinct cellular domains can function to determine cell polarity, define embryonic axes, or contribute to cellular memory. Although much is understood about how proteins move and are targeted in cells, our understanding of the mechanisms of RNA transport and localization are at an early stage.

Localized mRNAs have been observed in numerous cell types from yeast to humans (reviewed in ref. 1). In large polarized cells such as oocytes and early embryos, mRNA localization is an important mechanism for establishing embryonic axes and functioning as tissue determinants (2). In Drosophila, embryonic axis specification is determined by two localized mRNAs: bicoid, which is localized to the anterior pole, and nanos, which is localized to posterior pole (3). These localized RNAs set up opposing protein gradients that define the anterior and posterior axes of the embryo. VegT mRNA, a determinant for endoderm formation, must be localized to the vegetal pole during oogenesis in Xenopus to ensure normal establishment of embryonic germ layers (4). A striking example of RNA localization is found in the Ascidian Ciona intestinalis, where an mRNA, macho-1, which has been identified as a muscle determinant, is tightly localized to a region of the egg before fertilization and is asymmetrically segregated during early cleavage stages (5). Other examples of asymmetric segregation of mRNAs during cell division can be found in yeast and Drosophila. In yeast, asymmetrically segregated ASH1 mRNA determines mating type in the daughter cell during division (reviewed in ref. 6). In proliferating Drosophila neuroblasts, the homeobox transcription factor Prospero is asymmetrically localized to the basal side of the cell and segregated to the ganglion mother cell …