An erythrocyte-centric view on the MFSD2B sphingosine-1-phosphate transporter.
Pharmacol Ther
; 249: 108483, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37390971
ABSTRACT
MFSD2B has been identified as the exclusive sphingosine-1-phosphate (S1P) transporter in red blood cells (RBC) and platelets. MFSD2B-mediated S1P export from platelets is required for aggregation and thrombus formation, whereas RBC MFSD2B maintains plasma S1P levels in concert with SPNS2, the vascular and lymphatic endothelial cell S1P exporter, to control endothelial permeability and ensure normal vascular development. However, the physiological function of MFSD2B in RBC remains rather elusive despite mounting evidence that the intracellular S1P pool plays important roles in RBC glycolysis, adaptation to hypoxia and the regulation of cell shape, hydration, and cytoskeletal organisation. The large accumulation of S1P and sphingosine in MFSD2B-deficient RBC coincides with stomatocytosis and membrane abnormalities, the reasons for which have remained obscure. MFS family members transport substrates in a cation-dependent manner along electrochemical gradients, and disturbances in cation permeability are known to alter cell hydration and shape in RBC. Furthermore, the mfsd2 gene is a transcriptional target of GATA together with mylk3, the gene encoding myosin light chain kinase (MYLK). S1P is known to activate MYLK and thereby impact on myosin phosphorylation and cytoskeletal architecture. This suggests that metabolic, transcriptional and functional interactions may exist between MFSD2B-mediated S1P transport and RBC deformability. Here, we review the evidence for such interactions and the implications for RBC homeostasis.
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2023
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