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

Lee, Gun Hee; Fujita, Morihisa; Takaoka, Katsuyoshi; Murakami, Yoshiko; Fujihara, Yoshitaka; Kanzawa, Noriyuki; Murakami, Kei-Ichi; Kajikawa, Eriko; Takada, Yoko; Saito, Kazunobu; Ikawa, Masahito; Hamada, Hiroshi; Maeda, Yusuke; Kinoshita, Taroh

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

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

Lee, Gun Hee; Fujita, Morihisa; Takaoka, Katsuyoshi et al.

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

Number of Access:1,558（2025-08-13 22:44 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78593

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Title	A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO
Creator	CreatorName Lee, Gun Hee
	NRID 1000030532056 1000030532056 CreatorName Fujita, Morihisa
	NRID 1000090551044 1000090551044 CreatorName Takaoka, Katsuyoshi
	NRID 1000000304048 1000000304048 researchmap permalink read0191261 read0191261 Scopus Author ID 35725869400 35725869400 CreatorName Murakami, Yoshiko
	NRID 1000070578848 1000070578848 CreatorName Fujihara, Yoshitaka
	NRID 1000040452461 1000040452461 CreatorName Kanzawa, Noriyuki
	CreatorName Murakami, Kei-Ichi
	CreatorName Kajikawa, Eriko
	CreatorName Takada, Yoko
	CreatorName Saito, Kazunobu
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
	NRID 1000000208589 1000000208589 CreatorName Hamada, Hiroshi
	NRID 1000000294124 1000000294124 CreatorName Maeda, Yusuke
	NRID 1000010153165 1000010153165 researchmap permalink read0014310 read0014310 Scopus Author ID 35399558000 35399558000 CreatorName Kinoshita, Taroh
Description	©2016 Gun-Hee Lee et al. Originally published in Journal of Cell Biology. https://doi.org/10.1083/jcb.201605121
Abstract	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.
Publisher	Rockefeller University Press
Source Title	Journal of Cell Biology
Volume (Issue)	215(5)
Page	705-718
Date of Issued	2016-11-23
Language	English
Handle URL	https://hdl.handle.net/11094/78593
PISSN	00219525
eISSN	15408140
NCID	AA1203766X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1083/jcb.201605121
Relation.isIdenticalTo	PMID 27881714
Access Rights	open access
CopyRight	© 2016 Lee et al. This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Journal of Cell Biology. 2016, 215(5), p. 705-718
DC.title	A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO
DC.creator	Lee, Gun Hee
	Fujita, Morihisa
	Takaoka, Katsuyoshi
	Murakami, Yoshiko
	Fujihara, Yoshitaka
	Kanzawa, Noriyuki
	Murakami, Kei-Ichi
	Kajikawa, Eriko
	Takada, Yoko
	Saito, Kazunobu
	Ikawa, Masahito
	Hamada, Hiroshi
	Maeda, Yusuke
	Kinoshita, Taroh
DC.publisher	Rockefeller University Press
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2016-11-23
DC.identifier	https://doi.org/10.1083/jcb.201605121
DC.description	©2016 Gun-Hee Lee et al. Originally published in Journal of Cell Biology. https://doi.org/10.1083/jcb.201605121
DCTERMS.abstract	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.
DC.rights	© 2016 Lee et al. This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
DC.format	78593
citation_title	A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO
citation_author	Lee, Gun Hee
	Fujita, Morihisa
	Takaoka, Katsuyoshi
	Murakami, Yoshiko
	Fujihara, Yoshitaka
	Kanzawa, Noriyuki
	Murakami, Kei-Ichi
	Kajikawa, Eriko
	Takada, Yoko
	Saito, Kazunobu
	Ikawa, Masahito
	Hamada, Hiroshi
	Maeda, Yusuke
	Kinoshita, Taroh
citation_publisher	Rockefeller University Press
citation_language	English
citation_date	2016-11-23
citation_journal_title	Journal of Cell Biology
citation_volume	215
citation_issue	5
citation_firstpage	705
citation_lastpage	718
citation_doi	https://doi.org/10.1083/jcb.201605121
citation_pmid	27881714
citation_public_url	https://hdl.handle.net/11094/78593

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

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