学術雑誌論文

学術雑誌論文

Journal of Cell Biology. 2016, 215(5), p. 705-718

A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO

Rockefeller University Press

英語

2016-11-23

https://doi.org/10.1083/jcb.201605121

©2016 Gun-Hee Lee et al. Originally published in Journal of Cell Biology. https://doi.org/10.1083/jcb.201605121

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) can be shed from the cell membrane by GPI cleavage. In this study, we report a novel GPI-processing enzyme, termed post-glycosylphosphatidylinositol attachment to proteins 6 (PGAP6), which is a GPI-specific phospholipase A2 mainly localized at the cell surface. CRI PTO, a GPI-AP, which plays critical roles in early embryonic development by acting as a Nodal coreceptor, is a highly sensitive substrate of PGAP6, whereas CRY PTIC, a close homologue of CRI PTO, is not sensitive. CRI PTO processed by PGAP6 was released as a lysophosphatidylinositol-bearing form, which is further cleaved by phospholipase D. CRI PTO shed by PGAP6 was active as a coreceptor in Nodal signaling, whereas cell-associated CRI PTO activity was reduced when PGAP6 was expressed. Homozygous Pgap6 knockout mice showed defects in early embryonic development, particularly in the formation of the anterior-posterior axis, which are common features with Cripto knockout embryos. These results suggest PGAP6 plays a critical role in Nodal signaling modulation through CRI PTO shedding.

© 2016 Lee et al. This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

78593

A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO

Rockefeller University Press

英語

2016-11-23

Journal of Cell Biology

215

5

705

718

https://doi.org/10.1083/jcb.201605121

27881714

https://hdl.handle.net/11094/78593