Deletion of Mfsd2b impairs thrombotic functions of platelets
Autor: | Sneha Muralidharan, Long N. Nguyen, Thiet Minh Vu, Juat Chin Foo, Aaron Wei Liang Li, Mark Y. Chan, Toan Quoc Nguyen, Zafrul Hasan, Sang-Ha Baik, Madhuvanthi Chandrakanthan, Wei-Yi Ong, Amaury Cazenave-Gassiot, Markus R. Wenk, Sock Hwee Tan, Uyen Thanh Nha Le, Hoa Thi Thuy Ha, Federico Torta |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Blood Platelets
Male Platelets 0301 basic medicine Cytoplasm Platelet Function Tests Science General Physics and Astronomy 030204 cardiovascular system & hematology Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Fibrinolytic Agents Sphingosine medicine Animals Humans Platelet Platelet activation Thrombus Mice Knockout Venous Thrombosis Sphingolipids Multidisciplinary Protein transport Chemistry organic chemicals Membrane Proteins Transporter General Chemistry medicine.disease Sphingolipid Transport protein Cell biology Disease Models Animal 030104 developmental biology Knockout mouse lipids (amino acids peptides and proteins) Lysophospholipids |
Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021) Nature Communications |
ISSN: | 2041-1723 |
Popis: | We recently discovered that Mfsd2b, which is the S1P exporter found in blood cells. Here, we report that Mfsd2b is critical for the release of all S1P species in both resting and activated platelets. We show that resting platelets store S1P in the cytoplasm. After activation, this S1P pool is delivered to the plasma membrane, where Mfsd2b is predominantly localized for export. Employing knockout mice of Mfsd2b, we reveal that platelets contribute a minor amount of plasma S1P. Nevertheless, Mfsd2b deletion in whole body or platelets impairs platelet morphology and functions. In particular, Mfsd2b knockout mice show significantly reduced thrombus formation. We show that loss of Mfsd2b affects intrinsic platelet functions as part of remarkable sphingolipid accumulation. These findings indicate that accumulation of sphingolipids including S1P by deletion of Mfsd2b strongly impairs platelet functions, which suggests that the transporter may be a target for the prevention of thrombotic disorders. The mechanisms by which platelets release sphingosine-1-phosphate (S1P) is not well characterized. Here the authors show that Mfsd2b is required for S1P release from both resting and activated platelets and that deletion of Mfsd2b impairs thrombotic functions of platelets. |
Databáze: | OpenAIRE |
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