FIT2 organizes lipid droplet biogenesis with ER tubule-forming proteins and septins.
Animals
COS Cells
Caenorhabditis elegans
/ metabolism
Cell Line
Cell Line, Tumor
Chlorocebus aethiops
Endoplasmic Reticulum
/ metabolism
HEK293 Cells
Hep G2 Cells
Humans
Lipid Droplets
/ metabolism
Lipid Metabolism
/ physiology
Membrane Proteins
/ metabolism
Nogo Proteins
/ metabolism
Septins
/ metabolism
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
03 05 2021
03 05 2021
Historique:
received:
24
07
2019
revised:
29
12
2020
accepted:
09
02
2021
entrez:
16
4
2021
pubmed:
17
4
2021
medline:
29
9
2021
Statut:
ppublish
Résumé
Lipid droplets (LDs) are critical for lipid storage and energy metabolism. LDs form in the endoplasmic reticulum (ER). However, the molecular basis for LD biogenesis remains elusive. Here, we show that fat storage-inducing transmembrane protein 2 (FIT2) interacts with ER tubule-forming proteins Rtn4 and REEP5. The association is mainly transmembrane domain based and stimulated by oleic acid. Depletion of ER tubule-forming proteins decreases the number and size of LDs in cells and Caenorhabditis elegans, mimicking loss of FIT2. Through cytosolic loops, FIT2 binds to cytoskeletal protein septin 7, an interaction that is also required for normal LD biogenesis. Depletion of ER tubule-forming proteins or septins delays nascent LD formation. In addition, FIT2-interacting proteins are up-regulated during adipocyte differentiation, and ER tubule-forming proteins, septin 7, and FIT2 are transiently enriched at LD formation sites. Thus, FIT2-mediated nascent LD biogenesis is facilitated by ER tubule-forming proteins and septins.
Identifiants
pubmed: 33861319
pii: 211999
doi: 10.1083/jcb.201907183
pmc: PMC8056755
pii:
doi:
Substances chimiques
FITM2 protein, human
0
Membrane Proteins
0
Nogo Proteins
0
Septins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
Informations de copyright
© 2021 Chen et al.
Références
Cell. 2008 Dec 12;135(6):1098-107
pubmed: 19070579
J Cell Biol. 2013 Dec 23;203(6):985-1001
pubmed: 24368806
Elife. 2017 Mar 13;6:
pubmed: 28287394
J Cell Biol. 2018 Dec 3;217(12):4080-4091
pubmed: 30327422
J Biol Chem. 2015 Oct 16;290(42):25686-99
pubmed: 26304121
Science. 2008 Feb 29;319(5867):1247-50
pubmed: 18309084
J Lipid Res. 2000 Jul;41(7):1067-76
pubmed: 10884287
Cell. 2006 Feb 10;124(3):573-86
pubmed: 16469703
Lipids Health Dis. 2017 Jun 29;16(1):128
pubmed: 28662670
EMBO J. 2005 Jun 1;24(11):1931-41
pubmed: 15889145
J Mol Biol. 1999 Jul 2;290(1):99-117
pubmed: 10388560
Crit Rev Biochem Mol Biol. 2014 Jul-Aug;49(4):304-26
pubmed: 25039762
Science. 2015 Aug 28;349(6251):aab3500
pubmed: 26315442
Elife. 2014;3:e01607
pubmed: 24497546
Nat Genet. 2001 Jan;27(1):121-4
pubmed: 11138012
Nature. 2007 Sep 20;449(7160):311-5
pubmed: 17637674
J Cell Biol. 2015 Nov 23;211(4):829-44
pubmed: 26572621
Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3077-82
pubmed: 12629214
Nat Commun. 2017 Jul 06;8:15979
pubmed: 28681845
Curr Biol. 2018 Mar 19;28(6):915-926.e9
pubmed: 29526591
Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1945-51
pubmed: 16051877
FEBS Lett. 2008 Jan 9;582(1):90-6
pubmed: 18023282
Methods Cell Biol. 2016;136:199-220
pubmed: 27473911
Nat Cell Biol. 2014 Apr;16(4):322-34
pubmed: 24633326
PLoS One. 2010 Dec 23;5(12):e15030
pubmed: 21203462
Diabetologia. 2017 Feb;60(2):324-335
pubmed: 27866222
Mol Cell Proteomics. 2013 May;12(5):1115-26
pubmed: 23319140
Mol Biol Cell. 2015 Feb 15;26(4):726-39
pubmed: 25540432
Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):3976-81
pubmed: 21368113
Dev Cell. 2013 Feb 25;24(4):384-99
pubmed: 23415954
Cell Rep. 2013 May 30;3(5):1465-75
pubmed: 23684613
J Cell Biol. 2011 Mar 21;192(6):1043-55
pubmed: 21422231
Annu Rev Cell Dev Biol. 2017 Oct 6;33:491-510
pubmed: 28793795
Nat Commun. 2016 Jul 15;7:12203
pubmed: 27417143
J Cell Biol. 2004 Oct 11;167(1):35-41
pubmed: 15466483
J Cell Biol. 2015 Sep 14;210(6):961-72
pubmed: 26370501
Microb Cell. 2017 Dec 28;5(2):88-103
pubmed: 29417057
Elife. 2016 Aug 26;5:
pubmed: 27564575
Dev Cell. 2018 Oct 22;47(2):248-256.e4
pubmed: 30293840
J Cell Sci. 2020 Nov 5;133(21):
pubmed: 33033181
J Cell Sci. 2011 Jul 15;124(Pt 14):2424-37
pubmed: 21693588
Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):94-9
pubmed: 18160536
Nat Cell Biol. 2007 Sep;9(9):1089-97
pubmed: 17721513
Cell. 2010 Nov 24;143(5):774-88
pubmed: 21111237
Hum Mol Genet. 2016 Dec 1;25(23):5111-5125
pubmed: 27638887
Biochem J. 2009 Oct 23;424(1):61-7
pubmed: 19708857
Biochemistry. 2010 Dec 21;49(50):10747-55
pubmed: 21062080
J Cell Biol. 2015 Oct 26;211(2):261-71
pubmed: 26504167
Methods Cell Biol. 2013;116:1-14
pubmed: 24099284
Curr Biol. 2020 Jul 6;30(13):2481-2494.e6
pubmed: 32442467
Nat Rev Mol Cell Biol. 2006 May;7(5):373-8
pubmed: 16550215
J Biol Chem. 2014 Apr 4;289(14):9560-72
pubmed: 24519944
J Cell Biol. 2020 Oct 5;219(10):
pubmed: 32915949
Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20890-5
pubmed: 18093937
Hum Mutat. 2014 Apr;35(4):497-504
pubmed: 24478229
J Cell Biol. 2011 Nov 28;195(5):815-26
pubmed: 22123865
J Biol Chem. 2006 Nov 10;281(45):34537-48
pubmed: 16968695
Nat Protoc. 2013 Nov;8(11):2281-2308
pubmed: 24157548
EMBO J. 2016 Dec 15;35(24):2699-2716
pubmed: 27879284
Nat Rev Mol Cell Biol. 2007 Jul;8(7):519-29
pubmed: 17565364
Prog Lipid Res. 2001 Sep;40(5):325-438
pubmed: 11470496
Semin Liver Dis. 2013 Nov;33(4):312-20
pubmed: 24222089
Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19581-6
pubmed: 22106267
Cell. 2006 Aug 11;126(3):435-9
pubmed: 16901774
J Biol Chem. 2008 Jul 4;283(27):18892-904
pubmed: 18442980
Cell. 2009 Aug 7;138(3):549-61
pubmed: 19665976