ACBD3 is required for FAPP2 transferring glucosylceramide through maintaining the Golgi integrity

Journal of Molecular Cell Biology
Jing LiaoXinwang Cao

Abstract

Glycosphingolipid (GSL) metabolism is involved in various physiological processes, including all major cell signaling pathways, and its dysregulation is linked to some diseases. The four-phosphate adaptor protein FAPP2-mediated glucosylceramide (GlcCer) transport for complex GSL synthesis has been studied extensively. However, the molecular machinery of FAPP2 as a GlcCer-transferring protein remains poorly defined. Here, we identify a Golgi-resident protein, acyl-coenzyme A binding domain containing 3 (ACBD3), as an interacting partner of FAPP2. We find that ACBD3 knockdown leads to dramatic Golgi fragmentation, which subsequently causes FAPP2 dispersal throughout the cytoplasm and a decreased localization at trans-Golgi network. The further quantitative lipidomic analysis indicates that ACBD3 knockdown triggers abnormal sphingolipid metabolism. Interestingly, the expression of siRNA-resistant full-length ACBD3 can rescue these defects caused by ACBD3 knockdown. These data reveal critical roles for ACBD3 in maintaining the integrity of Golgi morphology and cellular sphingolipid homeostasis and establish the importance of the integrated Golgi complex for the transfer of GlcCer and complex GSL synthesis.

References

Nov 20, 2002·The Journal of Cell Biology·Raymond ChiuDennis Shields
Apr 27, 2004·Nature Cell Biology·Anna GodiM Antonietta De Matteis
Aug 17, 2005·The Journal of Cell Biology·Otilia V VieiraKai Simons
Jul 28, 2006·The Journal of Biological Chemistry·Juan I SbodioCarolyn E Machamer
Feb 7, 2007·Molecular and Cellular Endocrinology·Vassilios PapadopoulosMartine Culty
Aug 10, 2007·Nature·Giovanni D'AngeloMaria Antonietta De Matteis
Aug 23, 2007·The Journal of Biological Chemistry·Juan I Sbodio, Carolyn E Machamer
Oct 10, 2007·The Journal of Cell Biology·David HalterHein Sprong
Jan 2, 2010·Progress in Lipid Research·Jinjiang FanVassilios Papadopoulos
Apr 30, 2010·Nature·Hirofumi MaruyamaHideshi Kawakami
Dec 15, 2010·Journal of Molecular Cell Biology·Youjun ChuXuebiao Yao
Apr 20, 2011·Cold Spring Harbor Perspectives in Biology·Judith Klumperman
May 11, 2011·Cold Spring Harbor Perspectives in Biology·Clifford A Lingwood
Nov 30, 2011·The EMBO Journal·Jun SasakiKoki Taniguchi
Jun 20, 2012·Proceedings of the National Academy of Sciences of the United States of America·Regina Wai-Yan ChoyRandy Schekman
Jan 25, 2013·Molecular Biology of the Cell·Michelle M NgSeth J Field
Aug 6, 2013·Nature·Giovanni D'AngeloMaria Antonietta De Matteis
Oct 30, 2013·The FEBS Journal·Giovanni D'AngeloDomenico Russo
Feb 4, 2014·Cell·Suzette E Farber-KatzSeth J Field
Mar 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Gunjan JoshiYanzhuang Wang
Apr 23, 2015·Progress in Lipid Research·Ditte NeessNils J Færgeman
Oct 19, 2017·Journal of Molecular Cell Biology·Xiaoling BaoYunyu Shi
Nov 18, 2017·Nature Reviews. Cancer·Besim Ogretmen
Nov 23, 2017·Nature Reviews. Molecular Cell Biology·Yusuf A Hannun, Lina M Obeid

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Citations

Apr 27, 2019·International Journal of Molecular Sciences·Xihua YueIntaek Lee
May 28, 2019·Frontiers in Cell and Developmental Biology·Mario O CaracciMaría-Paz Marzolo
Jul 31, 2020·International Journal of Molecular Sciences·Cara-Lynne Schengrund
Jun 28, 2019·Frontiers in Cell and Developmental Biology·Andreas M ErnstJonathan S Bogan
Feb 12, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Markus IslingerMichael Schrader
Aug 3, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Anders P E Backman, Peter Mattjus

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