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The Protein Translocation Machinery of the Endoplasmic Reticulum: The Signal Hypothesis Ten Years Later

  • Peter Walter
  • Vivian Siegel
  • Leander Lauffer
  • Pablo D. Garcia
Part of the Springer Series in Molecular Biology book series (SSMOL)

Abstract

In 1975, the signal hypothesis was proposed by Blobel and Dobberstein to explain the targeting and translocation of secretory proteins across the endoplasmic reticulum (ER) membrane. Ten years later, molecular components of the cellular machinery catalyzing these events have been isolated and characterized. Our current view of the function of the signal recognition particle (SRP) and the SRP receptor (or docking protein) in the translocation of secretory and lysosomal proteins across—as well as integration of integral membrane proteins into—the ER membrane is described. In brief, SRP is thought to recognize the signal peptide on the nascent proteins and to arrest their translation in the cytoplasmic space. Upon interaction of the elongation-arrested ribosome with the correct target membrane (the ER), and particularly after a direct interaction of the ribosome-bound SRP with the SRP receptor in the ER membrane, the elongation arrest is released. A functional ribosome-membrane junction is established, allowing the translocation of the nascent polypeptide across the membrane by an as yet poorly understood mechanism.

In the last few years, major advances have been made in our understanding of the targeting and translocation machinery of the ER. Three distinct classes of proteins are known to utilize this translocation system: secretory (1) and lysosomal (2) proteins are translocated across the ER membrane, while certain classes of integral membrane proteins (3) are integrated into it. A detailed biochemical analysis of this process became feasible through the development of in vitro systems that were able to reproduce the translocation of nascent secretory proteins across the ER membrane (isolated in the form of closed microsomal vesicles) with apparent fidelity (4, 5). So far, two components have been purified from canine pancreas and shown to be required for the translocation event. We will introduce the reader to the biochemistry of these components and dicuss their role in protein translocation.

Keywords

Integral Membrane Protein Endoplasmic Reticulum Membrane Protein Translocation Microsomal Membrane Signal Recognition Particle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag New York Inc. 1986

Authors and Affiliations

  • Peter Walter
  • Vivian Siegel
  • Leander Lauffer
  • Pablo D. Garcia

There are no affiliations available

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