Regulation of glucosylceramide synthesis by Golgi-localized phosphoinositide

Yohei Ishibashi, Makoto Ito, Yoshio Hirabayashi

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Phosphoinositides mediate a large number of signaling processes in mammalian cells. Here, we report that phophatidylinositol-4-phosphate (PtdIns(4)P) downregulates the cellular glucosylceramide (GlcCer) level by inhibiting the interaction between GlcCer synthase (UGCG) and UDP-glucose in the Golgi apparatus. In this study, we used two PH domain probes to bind phosphoinositides; one derived from FAPP1 for targeting to the Golgi PtdIns(4)P and the other from PLC δ for targeting to the plasma membrane PtdIns(4,5)P2. The levels of GlcCer and lactosylceramide, but not of sphingomyelin (SM), were increased following expression of the FAPP1 PH domain in cells, accompanied by an increase in UGCG activity. However, no elevated GlcCer level was observed after expression of the PLC δ PH domain. PtdIns(4)P inhibited UGCG activity, but not SMS activity, in a concentration-dependent manner, and UGCG activity was restored by the addition of UDP-glucose in the reaction mixture. These results indicate that PtdIns(4)P inhibits UGCG activity by competing with UDP-glucose. We conclude that the increase in UGCG activity due to the expression of the FAPP1 PH domain was caused by an attenuation of the inhibitory effect of PtdIns(4)P on UGCG. This study provides new insights into the regulation of GlcCer synthesis by PtdIns(4)P in the Golgi apparatus.

元の言語英語
ページ(範囲)1011-1018
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
499
発行部数4
DOI
出版物ステータス出版済み - 5 23 2018

Fingerprint

Glucosylceramides
Phosphatidylinositols
Phosphates
Uridine Diphosphate Glucose
Golgi Apparatus
Programmable logic controllers
ceramide glucosyltransferase
Phosphatidylinositol 4,5-Diphosphate
Sphingomyelins
Cell membranes
Down-Regulation
Cells
Cell Membrane
Pleckstrin Homology Domains

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Regulation of glucosylceramide synthesis by Golgi-localized phosphoinositide. / Ishibashi, Yohei; Ito, Makoto; Hirabayashi, Yoshio.

:: Biochemical and Biophysical Research Communications, 巻 499, 番号 4, 23.05.2018, p. 1011-1018.

研究成果: ジャーナルへの寄稿記事

@article{5e4d25f9153d46e0ab2a6b9ac1e55602,
title = "Regulation of glucosylceramide synthesis by Golgi-localized phosphoinositide",
abstract = "Phosphoinositides mediate a large number of signaling processes in mammalian cells. Here, we report that phophatidylinositol-4-phosphate (PtdIns(4)P) downregulates the cellular glucosylceramide (GlcCer) level by inhibiting the interaction between GlcCer synthase (UGCG) and UDP-glucose in the Golgi apparatus. In this study, we used two PH domain probes to bind phosphoinositides; one derived from FAPP1 for targeting to the Golgi PtdIns(4)P and the other from PLC δ for targeting to the plasma membrane PtdIns(4,5)P2. The levels of GlcCer and lactosylceramide, but not of sphingomyelin (SM), were increased following expression of the FAPP1 PH domain in cells, accompanied by an increase in UGCG activity. However, no elevated GlcCer level was observed after expression of the PLC δ PH domain. PtdIns(4)P inhibited UGCG activity, but not SMS activity, in a concentration-dependent manner, and UGCG activity was restored by the addition of UDP-glucose in the reaction mixture. These results indicate that PtdIns(4)P inhibits UGCG activity by competing with UDP-glucose. We conclude that the increase in UGCG activity due to the expression of the FAPP1 PH domain was caused by an attenuation of the inhibitory effect of PtdIns(4)P on UGCG. This study provides new insights into the regulation of GlcCer synthesis by PtdIns(4)P in the Golgi apparatus.",
author = "Yohei Ishibashi and Makoto Ito and Yoshio Hirabayashi",
year = "2018",
month = "5",
day = "23",
doi = "10.1016/j.bbrc.2018.04.039",
language = "English",
volume = "499",
pages = "1011--1018",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Regulation of glucosylceramide synthesis by Golgi-localized phosphoinositide

AU - Ishibashi, Yohei

AU - Ito, Makoto

AU - Hirabayashi, Yoshio

PY - 2018/5/23

Y1 - 2018/5/23

N2 - Phosphoinositides mediate a large number of signaling processes in mammalian cells. Here, we report that phophatidylinositol-4-phosphate (PtdIns(4)P) downregulates the cellular glucosylceramide (GlcCer) level by inhibiting the interaction between GlcCer synthase (UGCG) and UDP-glucose in the Golgi apparatus. In this study, we used two PH domain probes to bind phosphoinositides; one derived from FAPP1 for targeting to the Golgi PtdIns(4)P and the other from PLC δ for targeting to the plasma membrane PtdIns(4,5)P2. The levels of GlcCer and lactosylceramide, but not of sphingomyelin (SM), were increased following expression of the FAPP1 PH domain in cells, accompanied by an increase in UGCG activity. However, no elevated GlcCer level was observed after expression of the PLC δ PH domain. PtdIns(4)P inhibited UGCG activity, but not SMS activity, in a concentration-dependent manner, and UGCG activity was restored by the addition of UDP-glucose in the reaction mixture. These results indicate that PtdIns(4)P inhibits UGCG activity by competing with UDP-glucose. We conclude that the increase in UGCG activity due to the expression of the FAPP1 PH domain was caused by an attenuation of the inhibitory effect of PtdIns(4)P on UGCG. This study provides new insights into the regulation of GlcCer synthesis by PtdIns(4)P in the Golgi apparatus.

AB - Phosphoinositides mediate a large number of signaling processes in mammalian cells. Here, we report that phophatidylinositol-4-phosphate (PtdIns(4)P) downregulates the cellular glucosylceramide (GlcCer) level by inhibiting the interaction between GlcCer synthase (UGCG) and UDP-glucose in the Golgi apparatus. In this study, we used two PH domain probes to bind phosphoinositides; one derived from FAPP1 for targeting to the Golgi PtdIns(4)P and the other from PLC δ for targeting to the plasma membrane PtdIns(4,5)P2. The levels of GlcCer and lactosylceramide, but not of sphingomyelin (SM), were increased following expression of the FAPP1 PH domain in cells, accompanied by an increase in UGCG activity. However, no elevated GlcCer level was observed after expression of the PLC δ PH domain. PtdIns(4)P inhibited UGCG activity, but not SMS activity, in a concentration-dependent manner, and UGCG activity was restored by the addition of UDP-glucose in the reaction mixture. These results indicate that PtdIns(4)P inhibits UGCG activity by competing with UDP-glucose. We conclude that the increase in UGCG activity due to the expression of the FAPP1 PH domain was caused by an attenuation of the inhibitory effect of PtdIns(4)P on UGCG. This study provides new insights into the regulation of GlcCer synthesis by PtdIns(4)P in the Golgi apparatus.

UR - http://www.scopus.com/inward/record.url?scp=85045409648&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045409648&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2018.04.039

DO - 10.1016/j.bbrc.2018.04.039

M3 - Article

C2 - 29627573

AN - SCOPUS:85045409648

VL - 499

SP - 1011

EP - 1018

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -