TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development

Yang Zhang, Trieu Le, Ryan Grabau, Zahra Mohseni, Hoejeong Kim, David R. Natale, Liping Feng, Hua Pan, Huanghe Yang

Aug 05, 2019

Received Date: 23rd July 19

Cell-cell fusion or syncytialization is fundamental to the reproduction, development and homeostasis of multicellular organisms. In addition to various cell-type specific fusogenic proteins, cell surface externalization of phosphatidylserine (PS), a universal eat-me signal in apoptotic cells, has been observed in different cell-fusion events. Nevertheless, molecular underpinnings of PS externalization and cellular mechanisms of PS-facilitated cell-cell fusion are unclear. Here we report that TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), plays an indispensable role in placental trophoblast fusion by translocating PS to the cell surface independent of apoptosis. Consistent with its essential role in trophoblast fusion, the placentas from TMEM16F-deficient mice exhibit deficiency in syncytialization, placental developmental defects and perinatal lethality. Our findings thus identify a cell-cell fusion mechanism by which TMEM16F CaPLSase-dependent externalization of PS serves as a critical cell fusion signal to facilitate trophoblast syncytialization and placental development.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature