Complex formation of sphingomyelin synthase 1 with glucosylceramide synthase increases sphingomyelin and decreases glucosylceramide levels

The Journal of Biological Chemistry
Yasuhiro HayashiAtsushi Yamashita

Abstract

Sphingolipids, including sphingomyelin (SM) and glucosylceramide (GlcCer), are generated by the addition of a polar head group to ceramide (Cer). Sphingomyelin synthase 1 (SMS1) and glucosylceramide synthase (GCS) are key enzymes that catalyze the conversion of Cer to SM and GlcCer, respectively. GlcCer synthesis has been postulated to occur mainly in cis-Golgi, and SM synthesis is thought to occur in medial/trans-Golgi; however, SMS1 and GCS are known to partially co-localize in cisternae, especially in medial/trans-Golgi. Here, we report that SMS1 and GCS can form a heteromeric complex, in which the N terminus of SMS1 and the C terminus of GCS are in close proximity. Deletion of the N-terminal sterile α-motif of SMS1 reduced the stability of the SMS1-GCS complex, resulting in a significant reduction in SM synthesis in vivo In contrast, chemical-induced heterodimerization augmented SMS1 activity, depending on an increase in the amount and stability of the complex. Fusion of the SMS1 N terminus to the GCS C terminus via linkers of different lengths increased SM synthesis and decreased GlcCer synthesis in vivo These results suggest that formation of the SMS1-GCS heteromeric complex increases SM synthesis and decreases GlcCer syn...Continue Reading

References

Apr 1, 1992·The Journal of Cell Biology·D JeckelF Wieland
May 14, 1996·Proceedings of the National Academy of Sciences of the United States of America·S IchikawaY Hirabayashi
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·S IchikawaY Hirabayashi
Dec 29, 1998·The Journal of Biological Chemistry·D L MarksR E Pagano
Oct 24, 2001·The Journal of Cell Biology·H SprongG van Meer
Jan 26, 2002·Molecular Biology of the Cell·Hisao NagayaHideo Kanoh
Nov 1, 2002·The Biochemical Journal·Wim J van BlitterswijkJannie Borst
Dec 5, 2002·The Journal of Biological Chemistry·Satoshi YasudaKentaro Hanada
Jul 12, 2003·The Journal of Biological Chemistry·F-Xabier ContrerasFélix M Goñi
Jul 15, 2003·Nature Structural Biology·Tzvi AvivCraig A Smibert
Sep 5, 2003·The Journal of Biological Chemistry·Francisco N BarreraJosé L Neira
Aug 1, 1959·Canadian Journal of Biochemistry and Physiology·E G BLIGH, W J DYER
Dec 9, 2003·Trends in Biochemical Sciences·Chongwoo A Kim, James U Bowie
Dec 20, 2003·Nature·Kentaro HanadaMasahiro Nishijima
Dec 20, 2003·The EMBO Journal·Klazien HuitemaJoost C M Holthuis
Apr 21, 2005·The Journal of Biological Chemistry·Etsuko KiyokawaToshihide Kobayashi
Jun 2, 2005·Science's STKE : Signal Transduction Knowledge Environment·Feng Qiao, James U Bowie
Jun 15, 2005·Trends in Cell Biology·Anthony H Futerman, Howard Riezman
Jun 28, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Cengiz OzalpByron Kemper
Oct 31, 2006·Biochimica Et Biophysica Acta·Félix M Goñi, Alicia Alonso
Apr 24, 2007·The Journal of Biological Chemistry·Fikadu Geta TafesseJoost C M Holthuis
Jun 8, 2007·Biochemical and Biophysical Research Communications·Susumu Mitsutake, Yasuyuki Igarashi
Aug 10, 2007·Nature·Giovanni D'AngeloMaria Antonietta De Matteis
Oct 10, 2007·The Journal of Cell Biology·David HalterHein Sprong
Aug 13, 2008·Biochimica Et Biophysica Acta·Calvin YeangXian-Cheng Jiang
Jun 10, 2009·The Journal of Cell Biology·Ana M VacaruJoost C M Holthuis
Jul 2, 2009·Journal of Chemical Biology·Lisa M Ballou, Richard Z Lin
Jun 29, 2010·Nature Biotechnology·Andrei V KarginovKlaus M Hahn
Jun 15, 2011·The Journal of Biological Chemistry·Susumu MitsutakeYasuyuki Igarashi
Sep 14, 2011·Biochimica Et Biophysica Acta·Edwin LiKalina Hristova
Feb 5, 2013·Vitamins and Hormones·Susumu Mitsutake, Yasuyuki Igarashi
Jun 19, 2013·Biochimica Et Biophysica Acta·Yohei IshibashiYoshio Hirabayashi
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Sep 19, 2014·The Journal of Biological Chemistry·Yasuhiro HayashiAtsushi Yamashita
Apr 11, 2015·Cell·Bei-Bei ChuBao-Liang Song

❮ Previous
Next ❯

Citations

Jul 10, 2019·International Journal of Molecular Sciences·Rossella Indellicato, Marco Trinchera
Sep 24, 2020·International Journal of Molecular Sciences·Alex E RyckmanJagdeep S Walia
Feb 6, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Zhiqiang LiXian-Cheng Jiang
Oct 8, 2020·Journal of Lipid and Atherosclerosis·Makoto Taniguchi, Toshiro Okazaki
Sep 14, 2021·The EMBO Journal·Prathyush PothukuchiSeetharaman Parashuraman
Oct 9, 2021·The Journal of Cell Biology·Jingjing ZhangBin Liang

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.