SIGNAL SEQUENCES SPECIFY THE TARGETING ROUTE TO THE ENDOPLASMIC-RETICULUM MEMBRANE

In the yeast Saccharomyces cerevisiae, only a subset of preproteins th at are translocated across the ER membrane require the function of the signal recognition particle (SRP), suggesting that an alternative, SR P-independent pathway must exist (Hann, B.C., and P. Waiter. 1991. Cel l. 67:131-144). We have established that the two targeting pathways fu nction in parallel. Mutant alleles of SEC62 and SEC63 were isolated th at specifically impaired the translocation of SRP-independent preprote ins in vivo and in vitro, whereas SRP-dependent preproteins were unaff ected. Based on this analysis, preproteins fall into three distinct cl asses: SRP dependent, SRP independent, and those that can use both pat hways. Pathway specificity is conferred by the hydrophobic core of sig nal sequences. Our studies show a previously unrecognized diversity in ER-directed signal sequences, that carry structural information that serves to identify the route taken.