Mechanisms Controlling the Activity of Localization Signal Sequences

All eukaryotic cells contain numerous membrane-enclosed compartments, such as nucleus, endoplasmic reticulum (ER), Golgi complex, mitochondria, endosomes, lysosomes, and peroxisomes. The function of each compartment is assured by a specific set of proteins. Since protein synthesis occurs primarily in the cytosol, accurate translocation and protein trafficking from the cytosol to their final destinations is essential to maintain proper cellular function and activity. Indeed, it has been estimated that at least half of the intracellular proteins have to be transported to their functional destination (Chacinska et al., 2009). To be at the right place at the right time, proteins use specific localization signal sequences to interact with the molecular partners deputed to guarantee their correct localization. For many years the function of these localization signals was considered as a housekeeping function, but a number of studies have revealed that fine molecular mechanisms may control the activity of signal sequences. Interestingly, many proteins do not have a single subcellular localization but are present in more cellular compartments. For some of them, multiple localizations are due to the generation of different mRNA forms by alternative splicing. However, most of the time, proteins can occupy multiple cellular locations without any change in the amino acid sequence, indicating the existence of regulatory mechanisms based on post-translational events (Carrie and Whelan, 2013). These events include post-translational modifications and signal exposing/masking switching mechanisms that regulate the interaction between signals and transport proteins. A number of evidences showing how the function of signal sequences can be controlled is illustrated and discussed in this article.