Standfirst
mRNAs encoding the individual components of the Arp2/3 complex, important for actin nucleation, are targeted to protrusions at the leading edge of migrating cells, and thereby provide an efficient means to generate this key complex locally.
Choices, choices. To target the translated protein product to its final destination, or to move the mRNA there and leave the rest to the local ribosomes? Mingle et al. have investigated how the actin-nucleating Arp2/3 complex finds itself at leading protrusions of migrating cells, and reveal the cell's choice in the Journal of Cell Science.
Mingle et al. began by confirming the localization of the Arp2/3 protein complex at cellular protrusions, and then explored the possibility that it is taken there through mRNA localization. By combining fluorescence in situ hybridization (FISH) and tyramide-signal amplification, the authors showed that all mRNAs for the seven subunits of Arp2/3 localized to the protrusions of human foreskin fibroblasts. The subunit mRNAs did not seem to colocalize, making it unlikely that they were co-transported as a complex, although this requires further investigation.
Mingle et al. then moved to chicken embryonic fibroblasts (CEFs) to assess whether the Arp2/3 subunit mRNAs move to the leading edge by default or in response to a specific stimulus. Depleting the cells of serum decreased the level of Arp2 mRNA expression and upset its distribution. Re-adding serum stimulated its expression and its localization at protrusions, implying that the Arp2/3 mRNA subunits probably localize in response to extracellular stimuli.
Other mRNAs that undergo specific targeting need assistance from the cytoskeleton for transport or anchoring, or both. To see whether this was the case for the Arp2/3 complex mRNAs, the actin or microtubule cytoskeletons were individually disrupted. Interfering with either filamentous network prevented the mRNAs from reaching their correct destination. Interestingly, 
-actin, which is also transported as an mRNA to protruding edges, needs just actin filaments.
So there are cellular 'tracks' on which the mRNAs move, but what provides the power? To address this question, the authors serum-starved CEFs and then treated them with BDM, a non-specific myosin inhibitor, at the same time as re-adding serum. This blocked Arp2 mRNA localization, as did adding the general myosin inhibitor H7 and the more specific inhibitors ML-7 (which inhibits myosin light-chain kinase) and blebbistatin (which is active against myosin-II). On the whole, the cell morphologies remained comparable to non-drug-treated cells, thereby ruling out an effect of changing cell morphology on mRNA localization. Myosin-II, then, is a prime candidate for localizing Arp2 mRNA.
This is the first report to show that the mRNAs encoding subunits of a protein complex can each be localized to the site of function. As Mingle et al. point out, this offers many advantages — not least that the localized synthesis of the individual parts of the multicomponent Arp2/3 complex increases the local concentration of the proteins in leading protrusions and therefore the likelihood that the outcome of any protein-protein rendez-vous in the area will be a success. Which will definitely enable things to move forward.
