Defining the physiological role of SRP in protein-targeting efficiency and specificity

When do you really need SRP? Proteins destined for the cell exterior are recruited during synthesis to the surface of the endoplasmic reticulum (ER) by the signal recognition particle (SRP). The classic view suggests that SRP recognizes signal sequences at the beginning of proteins. Working in yeast, Costa et al. found that many proteins with cleavable signal peptides were efficiently targeted during synthesis in the absence of SRP. In contrast, proteins with internal targeting signals universally depended on SRP and were susceptible to aberrant mitochondrial targeting in its absence. These studies establish the full physiological role of SRP in ensuring accurate and efficient protein targeting in the secretory pathway. Science , this issue p. 689