ArticleThe Journal of biological chemistry2018
Positive charge in the n-region of the signal peptide contributes to efficient post-translational translocation of small secretory preproteins.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Exploration of endogenous signal peptides and tandem linkage strategies for enhanced heterologous protein secretion inSynthetic and systems biotechnology · 2026Article
- Toward the Development of a Biosimilar Variant of Glucarpidase (Carboxypeptidase G2): Secretory Production, Optimization, and Immobilization.Molecular biotechnology · 2026Article
- A new form of diabetes caused by INS mutations defined by zygosity, stem cell and population data.EMBO molecular medicine · 2026Article
- Trapα deficiency impairs the early events of insulin biosynthesis and glucose homeostasis.The Journal of clinical investigation · 2025Article
- Signal Peptides: From Molecular Mechanisms to Applications in Protein and Vaccine Engineering.Biomolecules · 2025Review
- Efficient secretory production of recombinant proteins in microalgae using an exogenous signal peptide.Frontiers in microbiology · 2025Article
- Small HSPs at the crossroad between protein aggregation, autophagy and unconventional secretion: clinical implications and potential therapeutic opportunities in the context of neurodegenerative diseases.Frontiers in cell and developmental biology · 2025Review
- Role of Sec61α2 Translocon in Insulin Biosynthesis.Diabetes · 2024Article
- Loss of Preproinsulin Interaction with Signal Recognition Particle Activates Protein Quality Control, Decreasing mRNA Stability.Journal of molecular biology · 2024Article
- Signal peptide exchange alters HIV-1 envelope antigenicity and immunogenicity.Frontiers in immunology · 2024Article
- Pathogenic signal peptide variants in the human genome.NAR genomics and bioinformatics · 2023Article
- Characterization of signal and transit peptides based on motif composition and taxon-specific patterns.Scientific reports · 2023Article
- Review
- Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion.Biomolecules · 2023Review
- Comprehensive Analysis of Signal Peptides in Saccharomyces cerevisiae Reveals Features for Efficient Secretion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Heat shock protein Hspa13 regulates endoplasmic reticulum and cytosolic proteostasis through modulation of protein translocation.The Journal of biological chemistry · 2022Article
- Signal Peptide Variants in Inherited Retinal Diseases: A Multi-Institutional Case Series.International journal of molecular sciences · 2022Article
- Effects of a Shift of the Signal Peptide Cleavage Site in Signal Peptide Variant on the Synthesis and Secretion of SARS-CoV-2 Spike Protein.Molecules (Basel, Switzerland) · 2022Article
- The Bombyx mori Nucleopolyhedrovirus GP64 Retains the Transmembrane Helix of Signal Peptide to Contribute to Secretion across the Cytomembrane.Microbiology spectrum · 2022Article
- The Role of TRAPγ/SSR3 in Preproinsulin Translocation Into the Endoplasmic Reticulum.Diabetes · 2022Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Increasing evidence indicates that many small secretory preproteins can undergo post-translational translocation across the membrane of the endoplasmic reticulum. Although the cellular machinery involved in post-translational translocation of small secretory preproteins has begun to be elucidated, the intrinsic signals contained within these small secretory preproteins that contribute to their efficient post-translational translocation remain unknown. Here, we analyzed the eukaryotic secretory proteome and discovered the small secretory preproteins tend to have a higher probability to harbor the positive charge in the n-region of the signal peptide (SP). Eliminating the positive charge of the n-region blocked post-translational translocation of newly synthesized preproteins and selectively impaired translocation efficiency of small secretory preproteins. The pathophysiological significance of the positive charge in the n-region of SP was underscored by recently identified preproinsulin SP mutations that impair translocation of preproinsulin and cause maturity onset diabetes of youth (MODY). Remarkably, we have found that slowing the polypeptide elongation rate of small secretory preproteins could alleviate the translocation defect caused by loss of the n-region positive charge of the signal peptide. Together, these data reveal not only a previously unrecognized role of the n-region's positive charge in ensuring efficient post-translational translocation of small secretory preproteins, but they also highlight the molecular contribution of defects in this process to the pathogenesis of genetic disorders such as MODY.
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