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Title: Deletion of Mfsd2b impairs thrombotic functions of platelets
Authors: Chandrakanthan, Madhuvanthi
Toan, Quoc Nguyen
Hasan, Zafrul
Muralidharan, Sneha
Thiet, Minh Vu
Aaron, Wei Liang Li
Uyen, Thanh Nha Le
Hoa, Thi Thuy Ha
Baik, Sang-Ha 
Tan, Sock Hwee 
Foo, Juat Chin 
Wenk, Markus R 
Cazenave-Gassiot, Amaury
Torta, Federico
Ong, Wei Yi 
Chan, Mark Yan Yee 
Long, N Nguyen
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
Issue Date: 16-Apr-2021
Citation: Chandrakanthan, Madhuvanthi, Toan, Quoc Nguyen, Hasan, Zafrul, Muralidharan, Sneha, Thiet, Minh Vu, Aaron, Wei Liang Li, Uyen, Thanh Nha Le, Hoa, Thi Thuy Ha, Baik, Sang-Ha, Tan, Sock Hwee, Foo, Juat Chin, Wenk, Markus R, Cazenave-Gassiot, Amaury, Torta, Federico, Ong, Wei Yi, Chan, Mark Yan Yee, Long, N Nguyen (2021-04-16). Deletion of Mfsd2b impairs thrombotic functions of platelets. NATURE COMMUNICATIONS 12 (1). ScholarBank@NUS Repository.
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.
ISSN: 20411723
DOI: 10.1038/s41467-021-22642-x
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