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Incoming links: Microsomal protein import experiment
Protein targeting Created 2026-10-13 Updated 2026-10-18
Protein targeting directs a protein to its cellular destination. Synthesis in the cytosol does not imply that the protein works there.
For entry into the endoplasmic reticulum, distinguish three questions: does the nascent chain reach the membrane, does part of it cross into the ER lumen, and does a segment remain embedded as a transmembrane protein? Cotranslational protein translocation couples these events to biological translation. A signal peptide can initiate delivery without specifying the eventual destination of the mature protein.
Protein targeting to the endoplasmic reticulum: delivery and three possible outcomes
. Original pathway and membrane topology schematic. The upper row separates SRP recognition, membrane docking and passage through a translocon. Lower cartoons stipulate a soluble cargo, a cleaved signal peptide plus retained stop-transfer sequence, and an uncleaved internal signal anchor. Each drawn terminus is labeled; the internal-anchor orientation is one possibility. Shapes and lengths are illustrative, with no molecular coordinates or measured timings. Details.
This distinction matters experimentally. Finding a protein in a membrane-containing centrifugation pellet could reflect surface binding or protein aggregation. The microsomal protein import experiment instead asks whether an intact membrane prevents an external protease from reaching the product. That tests accessibility across a barrier, rather than proximity to it.
Signal peptide 2026-10-18
A signal peptide is a short targeting segment of a newly made polypeptide chain. A familiar ER signal sequence lies near the N-terminus and is removed during entry; Günter Blobel and Bernhard Dobberstein's 1975 experiments linked a larger immunoglobulin light chain precursor to a processed product.[ref]
Transfer of Proteins across Membranes I by Günter Blobel and Bernhard Dobberstein. Transfer of proteins across membranes. I, Introduction p. 836; Figures 5 and 14; Discussion pp. 845–847
Cleavage is a separate question from recognition. Not every targeting signal is a cleaved signal peptide: an internal signal anchor can remain part of a transmembrane protein. Conversely, loss of a segment does not by itself prove membrane crossing. Compare the independent size and accessibility readouts in the microsomal protein import experiment.