The potential O-linked glycosylation sites of C-X-C chemokine receptor type 4 mediate bone marrow homing of hematopoietic stem progenitor cells

The C-X-C chemokine receptor type 4 (CXCR4) and its ligand, C-X-C motif chemokine ligand 12 (CXCL12), are critical for the homing of hematopoietic stem progenitor cells (HSPCs) to bone marrow (BM). Our previous study revealed that carbohydrate chains on HSPCs are vital in the homing and engraftment of HSPCs. However, the relationship between the glycosylation of CXCR4 and HSCs homing remains unclear. In this study, we analyzed the glycosylation sites of the N-terminal 38 amino acids of CXCR4, which is indispensable for CXCL12 binding. Among these, simultaneous mutations of possible glycosylation sites, Serine-5 and Serine-9 of CXCR4 lost cell migration activity through CXCL12 in cultured cells. Furthermore, Serine-5 and Serine-9 mutations in HSPCs caused a deficiency in the homing to the BM. Our findings suggest that the glycosylation of CXCR4 is essential for homing HSCs to the BM, which can be used to screen cord blood HSCs suitable for transplantation.