Signal Sequences: The Same Yet Different

via its interaction with SRP receptor (reviewed by Walter and Johnson, 1994). Why then does the CPY signal se-Department of Chemistry University of Massachusetts at Amherst quence function in yeast? The finding that CPY translocates posttranslationally, Amherst, Massachusetts 01003 as does prepro-␣-factor, in a yeast in vitro translocation system (Hansen and Walter, 1988), suggested to Bird et al. that an SRP-independent pathway might be handling Signal sequences play a central role in the targeting and CPY export in yeast. Subsequent work has definitively translocation of nearly all secreted proteins and many shown that more than one efficient targeting pathway integral membrane proteins in both prokaryotes and eu-operates in yeast. The posttranslational process is ATP-karyotes, yet the molecular details of their involvement dependent, requires protein components on the mem-in these processes remain unclear. Considerable effort branes, is not coupled to protein synthesis, and is inde-has been expended to decipher the information that pendent of SRP (reviewed by Rapoport et al., 1996). these " zipcodes " present and to understand how it is While the existence of an SRP-independent pathway interpreted by the secretory machinery (for reviews, see in yeast is clear, these organisms also express compo-von Heijne, 1985; Gierasch, 1989). The notion has nents homologous to mammalian SRP (Hann and Wal-emerged that there are common features in signal se-ter, 1991). In vivo characterization of its function re-quences, despite their lack of sequence similarity, that vealed that, like its mammalian counterpart, yeast SRP is constitute the recognition motif interpreted by the tar-required for efficient translocation of secretory proteins geting machinery. Two striking observations support across the ER membrane. Interestingly, yeast SRP is this notion: many different signal sequences guide their not essential for cell growth. Therefore, SRP-facilitated passenger proteins through apparently common path-protein targeting to the ER membrane can be compen-ways, and signal sequences can be interchanged from sated by other targeting mechanisms, presumably post-one passenger protein to another in the same organism translational in nature. and from one organism to another. It is noteworthy that Yeast Signal Sequences Specify Their these generalizations are based on studies of quite a Targeting Pathway limited set of signal sequences and that they have be-Schekman and coworkers have shown that mutations come dogmatic despite a virtual absence of quantitative of yeast cellular components have differential effects characterization of the binding interactions of signal se-on translocated proteins, which provides an indication quences to their recognition components. …