Matches in SemOpenAlex for { <https://semopenalex.org/work/W2072773071> ?p ?o ?g. }
- W2072773071 abstract "PIKfyve is essential for the synthesis of phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P2] and for the regulation of endolysosomal membrane dynamics in mammals. PtdIns(3,5)P2 deficiency causes neurodegeneration in mice and humans, but the role of PtdIns(3,5)P2 in non-neural tissues is poorly understood. Here we show that platelet-specific ablation of PIKfyve in mice leads to accelerated arterial thrombosis, and, unexpectedly, also to inappropriate inflammatory responses characterized by macrophage accumulation in multiple tissues. These multiorgan defects are attenuated by platelet depletion in vivo, confirming that they reflect a platelet-specific process. PIKfyve ablation in platelets induces defective maturation and excessive storage of lysosomal enzymes that are released upon platelet activation. Impairing lysosome secretion from PIKfyve-null platelets in vivo markedly attenuates the multiorgan defects, suggesting that platelet lysosome secretion contributes to pathogenesis. Our findings identify PIKfyve as an essential regulator for platelet lysosome homeostasis, and demonstrate the contributions of platelet lysosomes to inflammation, arterial thrombosis and macrophage biology. PIKfyve is a lipid kinase essential for regulation of membrane homeostasis and vesicle trafficking along the endosomal-lysosomal pathway. Here the authors show that mice lacking PIKfyve exclusively in their platelets exhibit a systemic disorder characterized by multi-organ inflammation and thrombosis due to aberrant platelet lysosome function." @default.
- W2072773071 created "2016-06-24" @default.
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- W2072773071 date "2014-09-02" @default.
- W2072773071 modified "2023-10-16" @default.
- W2072773071 title "Loss of PIKfyve in platelets causes a lysosomal disease leading to inflammation and thrombosis in mice" @default.
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- W2072773071 cites W2023616745 @default.
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- W2072773071 cites W2036637585 @default.
- W2072773071 cites W2040983884 @default.
- W2072773071 cites W2045448846 @default.
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- W2072773071 doi "https://doi.org/10.1038/ncomms5691" @default.
- W2072773071 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4369914" @default.
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