Signal sequences specify the targeting route to the endoplasmic reticulum membrane

J Cell Biol. 1996 Jul;134(2):269-78. doi: 10.1083/jcb.134.2.269.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Biological Transport
  • DNA, Fungal
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / genetics
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Intracellular Membranes / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Protein Sorting Signals / genetics
  • Protein Sorting Signals / metabolism*
  • Saccharomyces cerevisiae / metabolism


  • DNA, Fungal
  • Protein Sorting Signals
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • dipeptidyl aminopeptidase B