A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.
Diabetes
ER chaperone
Insulin signaling
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
15 03 2023
15 03 2023
Historique:
received:
15
06
2022
accepted:
13
02
2023
entrez:
20
3
2023
pubmed:
21
3
2023
medline:
22
3
2023
Statut:
ppublish
Résumé
Neuropeptides, including insulin, are important regulators of physiological functions of the organisms. Trafficking through the Golgi is crucial for the regulation of secretion of insulin-like peptides. ASNA-1 (TRC40) and ENPL-1 (GRP94) are conserved insulin secretion regulators in Caenorhabditis elegans (and mammals), and mouse Grp94 mutants display type 2 diabetes. ENPL-1/GRP94 binds proinsulin and regulates proinsulin levels in C. elegans and mammalian cells. Here, we have found that ASNA-1 and ENPL-1 cooperate to regulate insulin secretion in worms via a physical interaction that is independent of the insulin-binding site of ENPL-1. The interaction occurs in DAF-28/insulin-expressing neurons and is sensitive to changes in DAF-28 pro-peptide levels. Consistently, ASNA-1 acted in neurons to promote DAF-28/insulin secretion. The chaperone form of ASNA-1 was likely the interaction partner of ENPL-1. Loss of asna-1 disrupted Golgi trafficking pathways. ASNA-1 localization to the Golgi was affected in enpl-1 mutants and ENPL-1 overexpression partially bypassed the ASNA-1 requirement. Taken together, we find a functional interaction between ENPL-1 and ASNA-1 that is necessary to maintain proper insulin secretion in C. elegans and provides insights into how their loss might cause diabetes in mammals.
Identifiants
pubmed: 36939052
pii: 297263
doi: 10.1242/dev.201035
pmc: PMC10112894
pii:
doi:
Substances chimiques
Arsenite Transporting ATPases
EC 3.6.3.16
ASNA-1 protein, C elegans
EC 3.6.3.16
Caenorhabditis elegans Proteins
0
Insulin
0
Proinsulin
9035-68-1
enpl-1 protein, C elegans
0
Molecular Chaperones
0
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 : Cancerfonden
Organisme : Vetenskapsrådet
Organisme : Stiftelsen Assar Gabrielssons Fond
Organisme : Göteborgs Universitet
Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
Références
Nat Chem Biol. 2013 Nov;9(11):677-84
pubmed: 23995768
Endocrinology. 2018 Feb 1;159(2):1062-1073
pubmed: 29272356
Nat Rev Dis Primers. 2015 Jul 23;1:15019
pubmed: 27189025
Mol Biol Cell. 2009 Mar;20(6):1855-64
pubmed: 19158397
J Cell Sci. 2011 Apr 15;124(Pt 8):1301-7
pubmed: 21444755
Cell. 2007 Feb 9;128(3):577-87
pubmed: 17289575
Biochim Biophys Acta. 2009 Feb;1793(2):239-52
pubmed: 19000718
FASEB J. 2012 Sep;26(9):3691-702
pubmed: 22649033
PLoS One. 2010 May 26;5(5):e10852
pubmed: 20520781
Development. 2014 Apr;141(8):1767-79
pubmed: 24671950
J Cell Sci. 2013 Apr 15;126(Pt 8):1785-95
pubmed: 23444385
Dev Biol. 2010 Mar 15;339(2):295-306
pubmed: 20044986
Nature. 2009 Sep 17;461(7262):361-6
pubmed: 19675567
J Biol Chem. 2013 Jun 21;288(25):18243-8
pubmed: 23671277
Cell. 2005 Nov 4;123(3):507-19
pubmed: 16269340
PLoS One. 2012;7(4):e34507
pubmed: 22511947
J Neurosci. 2011 Aug 10;31(32):11718-27
pubmed: 21832201
Development. 2015 Dec 15;142(24):4374-84
pubmed: 26552885
Development. 2018 Jan 3;145(1):
pubmed: 29180572
Gene. 2000 Jul 11;252(1-2):15-25
pubmed: 10903434
J Cell Sci. 2008 Jun 1;121(11):1832-40
pubmed: 18477612
Cell. 2008 Aug 22;134(4):634-45
pubmed: 18724936
Nat Rev Immunol. 2001 Nov;1(2):135-45
pubmed: 11905821
Diabetes. 1994 Apr;43(4):511-7
pubmed: 8138054
Sci Rep. 2021 Apr 21;11(1):8678
pubmed: 33883621
Biochem Biophys Res Commun. 2009 Oct 30;388(4):621-5
pubmed: 19686699
J Cell Sci. 2013 Jan 15;126(Pt 2):473-83
pubmed: 23203805
J Biol Chem. 2007 Dec 7;282(49):35612-20
pubmed: 17925398
Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11600-5
pubmed: 19553200
Development. 2020 Oct 27;147(20):
pubmed: 33037039
Bioessays. 2000 Jun;22(6):545-53
pubmed: 10842308
Circ Genom Precis Med. 2019 Sep;12(9):397-406
pubmed: 31461301
Diabetes. 2016 Jan;65(1):110-9
pubmed: 26438609
Cancer Res. 2010 Dec 15;70(24):10321-8
pubmed: 20966125
Curr Biol. 2006 Feb 21;16(4):421-7
pubmed: 16488878
PLoS Genet. 2009 Apr;5(4):e1000447
pubmed: 19343207
Worm. 2013 Jan 1;2(1):e24059
pubmed: 24058864
Cell. 2012 Mar 16;148(6):1160-71
pubmed: 22424227
Genetics. 1974 May;77(1):71-94
pubmed: 4366476
J Neurosci. 2001 Dec 1;21(23):9265-72
pubmed: 11717360
Genes Dev. 2001 Mar 15;15(6):672-86
pubmed: 11274053
J Biol Chem. 2019 Apr 19;294(16):6387-6396
pubmed: 30787103
Proc Natl Acad Sci U S A. 2022 Feb 1;119(5):
pubmed: 35078937
Curr Diabetes Rev. 2013 Jan 1;9(1):25-53
pubmed: 22974359
Genetics. 2021 Mar 31;217(3):
pubmed: 33677541
Blood. 2008 Aug 15;112(4):1223-30
pubmed: 18509083
Nat Cell Biol. 2008 Mar;10(3):272-82
pubmed: 18264092
J Cell Biol. 2008 Feb 11;180(3):483-91
pubmed: 18250196
Blood. 2010 Mar 25;115(12):2380-90
pubmed: 19965672
Semin Cell Dev Biol. 1999 Oct;10(5):495-505
pubmed: 10597632
Nat Methods. 2009 May;6(5):359-62
pubmed: 19377485
Cell. 2007 Mar 23;128(6):1147-59
pubmed: 17382883
J Mol Biol. 2021 Jun 25;433(13):166963
pubmed: 33811917
Nat Commun. 2010 Sep 21;1:79
pubmed: 20865800
Mol Cell Proteomics. 2012 Sep;11(9):710-23
pubmed: 22665516
J Neurosci. 2007 Jun 6;27(23):6150-62
pubmed: 17553987
Diabetes. 2019 Apr;68(4):747-760
pubmed: 30670477
PLoS Genet. 2022 Dec 8;18(12):e1010538
pubmed: 36480541
Mol Cell. 2014 Oct 2;56(1):116-27
pubmed: 25242142