A mechanism of self-lipid endocytosis mediated by the receptor Mincle
Year: 2022
Type: article
Abstract: Cellular lipid uptake (through endocytosis) is a basic physiological process. Dysregulation of this process underlies the pathogenesis of diseases such as atherosclerosis, obesity, diabetes, and cancer. However, to date, only some mechanisms of lipid endocytosis have been discovered. Here, we show a previously unknown mechanism of lipid cargo uptake into cells mediated by the receptor Mincle. We found that the receptor Mincle, previously shown to be a pattern recognition receptor of the innate immune system, tightly binds a range of self-lipids. Moreover, we revealed the minimal molecular motif in lipids that is sufficient for Mincle recognition. Superresolution microscopy showed that Mincle forms vesicles in cytoplasm and colocalizes with added fluorescent lipids in endothelial cells but does not colocalize with either clathrin or caveolin-1, and the added lipids were predominantly incorporated in vesicles that expressed Mincle. Using a model of ganglioside GM3 uptake in brain vessel endothelial cells, we show that the knockout of Mincle led to a dramatic decrease in lipid endocytosis. Taken together, our results have revealed a fundamental lipid endocytosis pathway, which we call Mincle-mediated endocytosis (MiME), and indicate a prospective target for the treatment of disorders of lipid metabolism, which are rapidly increasing in prevalence.
Authors: Alexey V. Kostarnoy, Petya G. Gancheva, Igor I. Kireev, Andrey I. Soloviev, Bernd Lepenies, Andrey Y. Kulibin, Ekaterina A. Malolina, Olga N. Scheglovitova, Alexey V. Kondratev, Maria V. Sokolova, Daria Vorobyeva, Nadezhda Filippova, Marina R. Kapkaeva, Maria A. Lagarkova, Pavel S. Metalnikov, Evgeniy Riabenko, Daniil A. Grumov, Maxim A. Bobrov, Elena Vasilieva, Boris S. Naroditsky, Alexander L. Gintsburg
Institutions: Gamalei Institute of Epidemiology and Microbiology, Lomonosov Moscow State University, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of the Ministry of Healthcare of the Russian Federation, University of Veterinary Medicine Hannover, Foundation, Russian Academy of Sciences, Koltzov Institute of Developmental Biology, Russian University of Medicine, Federal Medical-Biological Agency, Moscow Regional Scientific Research Clinical Institute. MF Vladimirsky
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4286586967