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Signal Peptide Features Determining the Substrate Specificities of Targeting and Translocation Components in Human ER
Sven Lang1, Duy Nguyen2, Pratiti Bhadra2
1Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
Frontiers in Physiology
|July 28, 2022
Summary
This study investigates how human cells target proteins to the endoplasmic reticulum (ER) using various pathways and components. Researchers used proteomics to understand protein targeting preferences under cellular conditions.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Approximately 30% of human polypeptides enter the secretory pathway via the endoplasmic reticulum (ER).
- ER import relies on signal peptides (SPs) or transmembrane helices (TMHs) and numerous cytosolic/ER proteins.
- Targeting mechanisms include cotranslational SRP/SR pathway and post-translational PEX, SND, or TRC pathways.
Purpose of the Study:
- To determine how precursor polypeptides select specific ER targeting pathways under physiological conditions.
- To elucidate the roles of auxiliary components like Sec62/63, TRAM1, and TRAP in protein translocation.
- To understand the client spectrum and specificities of ER import machinery.
Main Methods:
- Utilized siRNA-mediated depletion of targeting/transport components in HeLa cells.
- Employed label-free quantitative proteomics and differential protein abundance analysis.
- Integrated experimental findings with available structural data for mechanistic insights.
Main Results:
- Identified differential protein abundance patterns upon depletion of specific ER targeting factors.
- Provided insights into pathway preferences based on polypeptide features.
- Revealed client spectrum and specificities of auxiliary ER translocation components.
Conclusions:
- The study clarifies pathway selection for ER protein import in human cells.
- Findings shed light on the functional roles of accessory proteins in the Sec61 translocon.
- This research contributes to understanding the intricate mechanisms of protein translocation across the ER membrane.
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