Deletion of Mfsd2b impairs thrombotic functions of platelets

Madhuvanthi Chandrakanthan, Toan Quoc Nguyen, Zafrul Hasan, Sneha Muralidharan, Thiet Minh Vu, Aaron Wei Liang Li, Uyen Thanh Nha Le, Hoa Thuy Ha, Sang-Ha Baik, Sock Hwee Tan, Juat Chin Foo, Markus R. Wenk, Amaury Cazenave-Gassiot, Federico Torta, Wei Yi Ong, Mark Yan Yee Chan and Long N. Nguyen ()
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Madhuvanthi Chandrakanthan: National University of Singapore
Toan Quoc Nguyen: National University of Singapore
Zafrul Hasan: National University of Singapore
Sneha Muralidharan: National University of Singapore
Thiet Minh Vu: National University of Singapore
Aaron Wei Liang Li: National University of Singapore
Uyen Thanh Nha Le: National University of Singapore
Hoa Thuy Ha: National University of Singapore
Sang-Ha Baik: National University of Singapore
Sock Hwee Tan: National University of Singapore
Juat Chin Foo: National University of Singapore
Markus R. Wenk: National University of Singapore
Amaury Cazenave-Gassiot: National University of Singapore
Federico Torta: National University of Singapore
Wei Yi Ong: National University of Singapore
Mark Yan Yee Chan: National University of Singapore
Long N. Nguyen: National University of Singapore

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-22642-x

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