Cellular phosphatidic acid sensor, α-synuclein N-terminal domain, detects endogenous phosphatidic acid in macrophagic phagosomes and neuronal growth cones.
DGK, diacylglycerol kinase
DMEM, Dulbecco's modified Eagle's medium
Diacylglycerol kinase
F-actin, filamentous actin
FIPI, 5-fluoro-2-indolyl deschlorohalopemide
Growth cone
LPA, lysophosphatidic acid
LPAAT, LPA acyltransferase
Lipid sensor
Myr, myristoylated
PA, phosphatidic acid
PABD, phosphatidic acid-binding domain
PC, phosphatidylcholine
PLD, phospholipase D
Phagosome
Phosphatidic acid
Phospholipase D
α-Syn, α-synuclein
α-Syn-N, N-terminal region of α-Syn
α-Synuclein
Journal
Biochemistry and biophysics reports
ISSN: 2405-5808
Titre abrégé: Biochem Biophys Rep
Pays: Netherlands
ID NLM: 101660999
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
14
02
2020
accepted:
05
05
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
4
6
2020
Statut:
epublish
Résumé
Phosphatidic acid (PA) is the simplest phospholipid and is involved in the regulation of various cellular events. Recently, we developed a new PA sensor, the N-terminal region of α-synuclein (α-Syn-N). However, whether α-Syn-N can sense physiologically produced, endogenous PA remains unclear. We first established an inactive PA sensor (α-Syn-N-KQ) as a negative control by replacing all eleven lysine residues with glutamine residues. Using confocal microscopy, we next verified that α-Syn-N, but not α-Syn-N-KQ, detected PA in macrophagic phagosomes in which PA is known to be enriched, further indicating that α-Syn-N can be used as a reliable PA sensor in cells. Finally, because PA generated during neuronal differentiation is critical for neurite outgrowth, we investigated the subcellular distribution of PA using α-Syn-N. We found that α-Syn-N, but not α-Syn-N-KQ, accumulated at the peripheral regions (close to the plasma membrane) of neuronal growth cones. Experiments using a phospholipase D (PLD) inhibitor strongly suggested that PA in the peripheral regions of the growth cone was primarily produced by PLD. Our findings provide a reliable sensor of endogenous PA and novel insights into the distribution of PA during neuronal differentiation.
Identifiants
pubmed: 32490215
doi: 10.1016/j.bbrep.2020.100769
pii: S2405-5808(20)30078-9
pii: 100769
pmc: PMC7261706
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100769Informations de copyright
© 2020 The Authors.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest associated with the contents of this article.
Références
Trends Pharmacol Sci. 2015 Mar;36(3):137-44
pubmed: 25661257
Leuk Res. 2006 Aug;30(8):1027-36
pubmed: 16488473
J Biol Chem. 1995 Oct 27;270(43):25549-56
pubmed: 7592725
Biochim Biophys Acta. 2007 Jul;1771(7):793-806
pubmed: 17512245
J Biol Chem. 2017 Mar 10;292(10):4266-4279
pubmed: 28115519
J Neurosci. 2013 Dec 11;33(50):19470-9
pubmed: 24336713
Biochem Biophys Res Commun. 2019 Jun 11;513(4):1035-1040
pubmed: 31010675
Tohoku J Exp Med. 2008 Mar;214(3):199-212
pubmed: 18323690
EMBO J. 2009 Apr 22;28(8):1170-9
pubmed: 19229292
Biochem Biophys Rep. 2016 Oct 15;8:352-359
pubmed: 28955976
Pharmacol Rev. 2014 Oct;66(4):1033-79
pubmed: 25244928
Curr Opin Lipidol. 2018 Apr;29(2):110-115
pubmed: 29373329
Front Cell Dev Biol. 2016 Aug 17;4:82
pubmed: 27583247
Curr Drug Targets. 2008 Aug;9(8):626-40
pubmed: 18691010
J Phys Chem B. 2015 Apr 9;119(14):4812-23
pubmed: 25790164
Biochim Biophys Acta. 2009 Jun;1790(6):416-24
pubmed: 19364481
J Biol Chem. 2004 Jul 2;279(27):28603-13
pubmed: 15102830
Brain Res. 2015 Jan 12;1594:36-45
pubmed: 25446448
Biochimie. 2014 Dec;107 Pt A:51-7
pubmed: 25111738
J Biol Chem. 2014 Sep 19;289(38):26607-17
pubmed: 25112873
Neurochem Int. 2020 Mar;134:104645
pubmed: 31891737
Science. 2001 Nov 30;294(5548):1942-5
pubmed: 11729323
J Cell Biochem. 2007 Jan 1;100(1):191-203
pubmed: 16924673
Mol Cell Biol. 2005 Aug;25(16):7289-302
pubmed: 16055737
Lipids. 2019 Nov;54(11-12):763-771
pubmed: 31736090
Trends Neurosci. 2012 Mar;35(3):164-74
pubmed: 22154154
Acta Physiol (Oxf). 2012 Feb;204(2):219-26
pubmed: 21447092
Traffic. 2006 Mar;7(3):365-77
pubmed: 16497229
Cancer Res. 2005 Oct 15;65(20):9415-25
pubmed: 16230405
Biochem Biophys Rep. 2019 Jun 25;19:100660
pubmed: 31297456
FEBS J. 2020 Jun;287(11):2212-2234
pubmed: 31722116
J Neurochem. 2003 Mar;84(5):1051-65
pubmed: 12603829
Biochim Biophys Acta. 2006 Aug;1761(8):913-26
pubmed: 16624617
FEBS Lett. 2017 Mar;591(5):784-791
pubmed: 28186641
Adv Biol Regul. 2018 Jan;67:101-108
pubmed: 28918129
Biochem J. 2008 Jan 1;409(1):1-18
pubmed: 18062770