Natural killer (NK) cells play a vital role in the defense against viral infections and tumor development. NK cell function is primarily regulated by the sum of signals from a broad array of activation and inhibitory receptors. Key to generating the input level of either activating or inhibitory signals is the maintenance of receptor expression levels on the cell surface. Although the mechanisms of endocytosis and trafficking for some cell surface receptors, such as transferrin receptor and certain immune receptors, are very well known, that is not the situation for receptors expressed by NK cells. Recent studies have uncovered that endocytosis and trafficking routes characteristic for specific activation and inhibitory receptors can regulate the functional responses of NK cells. In this review, we summarize the current knowledge of receptor endocytosis and trafficking, and integrate this with our current understanding of NK cell receptor trafficking.
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http://dx.doi.org/10.1111/j.1600-0854.2009.00973.x | DOI Listing |
ACS Cent Sci
January 2025
Centre for Inflammation Research, The University of Edinburgh, EH16 4UU Edinburgh, U.K.
The cellular uptake routes of peptides and proteins are complex and diverse, often handicapping therapeutic success. Understanding their mechanisms of internalization requires chemical derivatization with approaches that are compatible with wash-free and real-time imaging. In this work, we developed a new late-stage labeling strategy for unprotected peptides and proteins, which retains their biological activity while enabling live-cell imaging of uptake and intracellular trafficking.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Pathology, Division of Microbiology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375, Wroclaw, Poland.
The process of viral entry into host cells is crucial for the establishment of infection and the determination of viral pathogenicity. A comprehensive understanding of entry pathways is fundamental for the development of novel therapeutic strategies. Standard techniques for investigating viral entry include confocal microscopy and flow cytometry, both of which provide complementary qualitative and quantitative data.
View Article and Find Full Text PDFJ Biol Chem
January 2025
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8; Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON, Canada, M5G 2M9. Electronic address:
The NUMB gene encodes a conserved adaptor protein with roles in asymmetric cell division and cell fate determination. First described as an inhibitor of Notch signaling, multi-functional NUMB proteins regulate multiple cellular pathways through protein complexes with ubiquitin ligases, polarity proteins and the endocytic machinery. The vertebrate NUMB protein isoforms were identified over two decades ago, yet the majority of functional studies exploring NUMB function in endocytosis, cell migration and adhesion, development and disease have largely neglected the potential for distinct isoform activity in design and interpretation.
View Article and Find Full Text PDFJ Neurochem
January 2025
Centre for Discovery Brain Sciences, Hugh Robson Building, George Square, University of Edinburgh, Edinburgh, Scotland, UK.
Synaptic vesicle protein 2A (SV2A) is an abundant synaptic vesicle cargo with an as yet unconfirmed role in presynaptic function. It is also heavily implicated in epilepsy, firstly being the target of the leading anti-seizure medication levetiracetam and secondly with loss of function mutations culminating in human disease. A range of potential presynaptic functions have been proposed for SV2A; however its interaction with the calcium sensor for synchronous neurotransmitter release, synaptotagmin-1 (Syt1), has received particular attention over the past decade.
View Article and Find Full Text PDFCells
January 2025
Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Pablo de Olavide, Américo Vespucio 24, 41092 Sevilla, Spain.
Lysosomes are subcellular compartments characterised by an acidic pH, containing an ample variety of acid hydrolases involved in the recycling of biopolymers. Among these hydrolases, lysosomal proteases have merely been considered as end-destination proteases responsible for the digestion of waste proteins, trafficked to the lysosomal compartment through autophagy and endocytosis. However, recent reports have started to unravel specific roles for these proteases in the regulation of initially unexpected biological processes, both under physiological and pathological conditions.
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