ArticleMolecular cell2016
Inverting the Topology of a Transmembrane Protein by Regulating the Translocation of the First Transmembrane Helix.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Deciphering the membrane topology of the pestiviral non-structural protein 4B (NS4B).Journal of virology · 2025Article
- Betagenin ameliorates diabetes by inducing insulin secretion and β-cell proliferation.The Journal of biological chemistry · 2025Article
- Secretion of endoplasmic reticulum protein VAPB/ALS8 requires topological inversion.Nature communications · 2024Article
- CLN3 transcript complexity revealed by long-read RNA sequencing analysis.BMC medical genomics · 2024Article
- Ceramide microdomains: the major influencers of the sphingolipid media platform.Biochemical Society transactions · 2024Review
- Isorhamnetin inhibits hypertrophic scar formation through TGF-β1/Smad and TGF-β1/CREB3L1 signaling pathways.Heliyon · 2024Article
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- TM4SF19 controls GABP-dependentProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Quantitative Mass Spectrometry Characterizes Client Spectra of Components for Targeting of Membrane Proteins to and Their Insertion into the Membrane of the Human ER.International journal of molecular sciences · 2023Review
- Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence.Cell reports · 2023Article
- Proteome-Wide Detection and Annotation of Receptor Tyrosine Kinases (RTKs): RTK-PRED and the TyReK Database.Biomolecules · 2023Article
- Overview of Sigma-1R Subcellular Specific Biological Functions and Role in Neuroprotection.International journal of molecular sciences · 2023Review
- Mechanism of Protein Translocation by the Sec61 Translocon Complex.Cold Spring Harbor perspectives in biology · 2023Review
- Abnormal plasma ceramides refine high-risk patients with worsening heart failure.Frontiers in cardiovascular medicine · 2023Article
- Transcriptome Response of Differentiating Muscle Satellite Cells to Thermal Challenge in Commercial Turkey.Genes · 2022Article
- You aren't IMMUNE to the ceramides that accumulate in cardiometabolic disease.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Article
- Ceramides and other sphingolipids as drivers of cardiovascular disease.Nature reviews. Cardiology · 2021Review
- Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex.Cells · 2021Review
- TRAM1 protein may support ER protein import by modulating the phospholipid bilayer near the lateral gate of the Sec61-channel.Channels (Austin, Tex.) · 2020Article
- Transcription factors activated through RIP (regulated intramembrane proteolysis) and RAT (regulated alternative translocation).The Journal of biological chemistry · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
TM4SF20 (transmembrane 4 L6 family 20) is a polytopic membrane protein that inhibits proteolytic processing of CREB3L1 (cAMP response element-binding protein 3-like 1), a membrane-bound transcription factor that blocks cell division and activates collagen synthesis. Here we report that ceramide stimulates CREB3L1 cleavage by inverting the orientation of TM4SF20 in membranes. In the absence of ceramide, the N terminus of the first transmembrane helix of TM4SF20 is inserted into the endoplasmic reticulum (ER) lumen. This translocation requires TRAM2 (translocating chain-associated membrane protein 2), a membrane protein containing a putative ceramide-interacting domain. In the presence of ceramide, the N terminus of the first transmembrane domain of TM4SF20 is exposed to cytosol. Consequently, the membrane topology of TM4SF20 is inverted, and this form of TM4SF20 stimulates CREB3L1 cleavage. In the presence of ceramide, translocation of TM4SF20 is TRAM2-independent. We designate this mechanism-causing regulated inversion of the membrane topology as "regulated alternative translocation."
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.