| Autor: |
Kostarnoy AV; Laboratory of Rickettsial Ecology, N. F. Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Gancheva PG; Laboratory of Immunobiotechnology, N. F. Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Kireev II; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.; Laboratory of Genetic Mechanisms of Development, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, 117997 Moscow, Russia., Soloviev AI; Laboratory of Detection and Ultrastructural Analysis of Microorganisms, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Lepenies B; Immunology Unit, Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, 30559 Hannover, Germany., Kulibin AY; Laboratory of Evolutionary Developmental Biology, Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 119071 Moscow, Russia., Malolina EA; Laboratory of Evolutionary Developmental Biology, Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 119071 Moscow, Russia., Scheglovitova ON; Laboratory of Antiviral Immunity, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Kondratev AV; Laboratory of Rickettsial Ecology, N. F. Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Sokolova MV; Laboratory of Mediators and Effectors of Immunity, N. F. Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Vorobyeva D; Laboratory of Atherothrombosis, Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia., Filippova N; Laboratory of Antiviral Immunity, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Kapkaeva MR; Laboratory of Antiviral Immunity, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Lagarkova MA; Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical-Biological Agency, 119435 Moscow, Russia., Metalnikov PS; Laboratory of Rickettsial Ecology, N. F. Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Riabenko E; Laboratory of Rickettsial Ecology, N. F. Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Grumov DA; Laboratory of Rickettsial Ecology, N. F. Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Bobrov MA; Laboratory of Rickettsial Ecology, N. F. Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia.; Department of Pathology, M. F. Vladimirsky Moscow Regional Clinical Research Institute, 129110 Moscow, Russia., Vasilieva E; Laboratory of Atherothrombosis, Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia., Naroditsky BS; Laboratory of Immunobiotechnology, N. F. Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Gintsburg AL; Laboratory of Gene Engineering of Pathogenic Microorganisms, N. F. Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia. |
| Abstrakt: |
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. |
