Signal sequences specify the targeting route to the endoplasmic reticulum membrane

doi:10.1083/jcb.134.2.269

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Signal sequences specify the targeting route to the endoplasmic reticulum membrane

DT Ng, JD Brown and P Walter
Department of Biochemistry and Biophysics, University of California, School of Medicine, San Francisco 94143-0448, USA. ng@cgl.ucsf.edu

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