Early endosomes represent first-line sorting compartments or even organelles for internalized molecules. They enable the transport of molecules or ligands to other compartments of the cell, such as lysosomes, for degradation or recycle them back to the membrane by various mechanisms. Moreover, early endosomes function as signaling and scaffolding platforms to initiate or prolong distinct signaling pathways. Accordingly, early endosomes have to be recognized as either part of a degradation or recycling pathway. The physical proximity of many ligand-binding receptors with other membrane-bound proteins or complexes such as NADPH oxidases may result in an interaction of second messengers, like reactive oxygen species (ROS) and early endosomes, that promote the correct recognition of individual early endosomes. In fact, redoxosomes comprise an endosomal subsection of signaling endosomes. One example of such potential interaction is epidermal growth factor receptor (EGFR) signaling. Here we summarize recent findings on EGFR signaling as a well-studied example for receptor trafficking and -activation and illustrate the interplay between cellular and endosomal ROS.
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http://dx.doi.org/10.3390/antiox13101215 | DOI Listing |
Expert Opin Drug Deliv
January 2025
Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Macclesfield, UK.
Introduction: mRNA therapeutics were a niche area in drug development before COVIDvaccines. Now they are used in vaccine development, for non-viral therapeuticgenome editing, chimericantigen receptor T (CAR T) celltherapies and protein replacement. mRNAis large, charged, and easily degraded by nucleases.
View Article and Find Full Text PDFHaematologica
January 2025
Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Bonn.
Von Willebrand factor (VWF) plays a critical role in hemostasis, and emerging evidence suggests its involvement in inflammation. Our study aimed to investigate the interaction between circulating plasma VWF and neutrophils (polymorphonuclear cells, PMNs), elucidate the fate of VWF after binding, and explore its impact on neutrophil behavior. Neutrophils were isolated from the whole blood of healthy volunteers, and their interaction with plasma VWF was examined ex vivo.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Department of Neuroscience, Yale Medical School, New Haven, Connecticut, USA.
Aging rhesus macaques provide a unique model for learning how age and inflammation drive early-stage pathology in sporadic Alzheimer's disease, and for testing potential therapeutics. Unlike mice, aging macaques have extensive association cortices and inflammatory signaling similar to humans, are apolipoprotein E ε4 homozygotes, and naturally develop tau and amyloid pathology with marked cognitive deficits. Importantly, monkeys provide the unique opportunity to study early-stage, soluble hyperphosphorylated tau (p-tau), including p-tau217.
View Article and Find Full Text PDFJ Cell Sci
January 2025
Laboratory of Cell Death & Cell Survival, Centre for DNA Fingerprinting and Diagnostics (CDFD), Uppal, Hyderabad 500039, India.
PPTC7 is a mitochondrial phosphatase that is essential for mitochondrial biogenesis, metabolism, protein content maintenance and transport. While the mitochondrial roles of PPTC7 are well-characterized, its roles outside the mitochondria are unclear. Here we identified a non-mitochondrial role for PPTC7 in regulating epidermal growth factor receptor (EGFR) trafficking.
View Article and Find Full Text PDFPathogens
November 2024
Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA.
RNA virus-induced excessive inflammation and impaired antiviral interferon (IFN-I) responses are associated with severe disease. This innate immune response, also referred to as "dysregulated immunity" is caused by viral single-stranded RNA (ssRNA)- and double-stranded-RNA (dsRNA)-mediated exuberant inflammation and viral protein-induced IFN antagonism. However, key host factors and the underlying mechanism driving viral RNA-mediated dysregulated immunity are poorly defined.
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