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Elucidation of the late steps in the glycan-dependent ERAD of soluble misfolded glycoproteins.
Plant J
January 2025
Department of Applied Genetics and Cell Biology, Institute of Plant Biotechnology and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, Vienna, A-1190, Austria.
The endoplasmic reticulum (ER) utilizes ER-associated degradation (ERAD), a highly conserved eukaryotic pathway, to eliminate misfolded or unassembled proteins and maintain protein homeostasis in cells. The clearance of misfolded glycoproteins involves several distinct steps, including the recognition of a specific glycan signal, retrotranslocation to the cytosol, and subsequent degradation of the misfolded protein by the ubiquitin proteasome system. Confocal microscopy was used to track the fate of a well-characterized ERAD substrate via a self-complementing split fluorescent protein assay.
View Article and Find Full Text PDFNEMF-mediated CAT-tailing defines distinct branches of translocation-associated quality control.
bioRxiv
August 2024
Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Ribosome stalling during co-translational translocation at the endoplasmic reticulum (ER) causes translocon clogging and impairs ER protein biogenesis. Mammalian cells resolve translocon clogging vial a poorly characterized translocation-associated quality control (TAQC) process. Here, we combine genome-wide CRISPR screen with live cell imaging to dissect the molecular linchpin of TAQC.
View Article and Find Full Text PDFImpact of interrupting antiretroviral therapy started during primary HIV-1 infection on plasma neurofilament light chain protein, a marker of neuronal injury: The SPARTAC trial.
J Virus Erad
June 2024
Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom.
Article Synopsis
- The study investigates the effects of antiretroviral therapy (ART) interruption on neuro-axonal injury, specifically measuring levels of neurofilament light protein (NfL) in individuals during primary HIV-1 infection.
- Findings show that NfL decreased after 48 weeks of ART, indicating reduced neuronal injury, and remained stable despite viral rebound after ART interruption.
- Additionally, baseline NfL levels correlated with higher plasma HIV-1 RNA and older age but showed no significant relationship with inflammation markers like IL-6 or total HIV-1 DNA.
Membralin is required for maize development and defines a branch of the endoplasmic reticulum-associated degradation pathway in plants.
Proc Natl Acad Sci U S A
June 2024
The Key Laboratory of Plant Development and Environment Adaptation Biology, Ministry of Education, School of Life Science, Shandong University, Qingdao 266237, China.
Endoplasmic reticulum (ER)-associated degradation (ERAD) plays key roles in controlling protein levels and quality in eukaryotes. The Ring Finger Protein 185 (RNF185)/membralin ubiquitin ligase complex was recently identified as a branch in mammals and is essential for neuronal function, but its function in plant development is unknown. Here, we report the map-based cloning and characterization of (), which encodes the ER membrane-localized protein membralin and specifically interacts with maize homologs of RNF185 and related components.
View Article and Find Full Text PDFProinsulin degradation and presentation of a proinsulin B-chain autoantigen involves ER-associated protein degradation (ERAD)-enzyme UBE2G2.
PLoS One
May 2024
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Type 1 diabetes (T1D) is characterized by HLA class I-mediated presentation of autoantigens on the surface of pancreatic β-cells. Recognition of these autoantigens by CD8+ T cells results in the destruction of pancreatic β-cells and, consequently, insulin deficiency. Most epitopes presented at the surface of β-cells derive from the insulin precursor molecule proinsulin.
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