Deletion of a flippase subunit Tmem30a in hematopoietic cells impairs mouse fetal liver erythropoiesis

• Published in: Haematologica (Roma) Vol. 104; no. 10; pp. 1984 - 1994
• Main Authors: Yang, Fan, Huang, Yumin, Chen, Xianda, Liu, Lu, Liao, Dandan, Zhang, Huan, Huang, Gang, Liu, Wenjing, Zhu, Xianjun, Wang, Wengong, Lobo, Cheryl A, Yazdanbakhsh, Karina, An, Xiuli, Ju, Zhenyu
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.10.2019
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2018.203992

Transmembrane protein 30A ( ) is the β-subunit of P4-ATPases which function as flippase that transports aminophospholipids such as phosphatidylserine from the outer to the inner leaflets of the plasma membrane to maintain asymmetric distribution of phospholipids. It has been documented that deficiency of led to exposure of phosphatidylserine. However, the role of remains largely unknown. Here we found that Vav-Cre-driven conditional deletion of in hematopoietic cells led to embryonic lethality due to severe anemia by embryonic day 16.5. The numbers of erythroid colonies and erythroid cells were decreased in the deficient fetal liver. This was accompanied by increased apoptosis of erythroid cells. Confocal microscopy analysis revealed an increase of localization of erythropoietin receptor to areas of membrane raft microdomains in response to erythropoietin stimulation in Ter119 erythroid progenitors, which was impaired in deficient cells. Moreover, erythropoietin receptor (EPOR)-mediated activation of the STAT5 pathway was significantly reduced in deficient fetal liver cells. Consistently, knockdown of in human CD34 cells also impaired erythropoiesis. Our findings demonstrate that plays a critical role in erythropoiesis by regulating the EPOR signaling pathway through the formation of membrane rafts in erythroid cells.