Progranulin deficiency leads to reduced glucocerebrosidase activity.
Animals
Cell Line
Disease Models, Animal
Female
Frontotemporal Lobar Degeneration
/ genetics
Glucosylceramidase
/ genetics
HEK293 Cells
Haploinsufficiency
Humans
Lysosomes
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation
Neuronal Ceroid-Lipofuscinoses
/ genetics
Progranulins
/ deficiency
Recombinant Proteins
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
31
01
2019
accepted:
19
06
2019
entrez:
11
7
2019
pubmed:
11
7
2019
medline:
19
2
2020
Statut:
epublish
Résumé
Mutation in the GRN gene, encoding the progranulin (PGRN) protein, shows a dose-dependent disease correlation, wherein haploinsufficiency results in frontotemporal lobar degeneration (FTLD) and complete loss results in neuronal ceroid lipofuscinosis (NCL). Although the exact function of PGRN is unknown, it has been increasingly implicated in lysosomal physiology. Here we report that PGRN interacts with the lysosomal enzyme, glucocerebrosidase (GCase), and is essential for proper GCase activity. GCase activity is significantly reduced in tissue lysates from PGRN-deficient mice. This is further evidence that reduced lysosomal hydrolase activity may be a pathological mechanism in cases of GRN-related FTLD and NCL.
Identifiants
pubmed: 31291241
doi: 10.1371/journal.pone.0212382
pii: PONE-D-19-03091
pmc: PMC6619604
doi:
Substances chimiques
GRN protein, human
0
Grn protein, mouse
0
Progranulins
0
Recombinant Proteins
0
Glucosylceramidase
EC 3.2.1.45
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
Pagination
e0212382Subventions
Organisme : NIA NIH HHS
ID : F32 AG027647
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS088448
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS095954
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
PLoS One. 2015 Sep 29;10(9):e0138107
pubmed: 26418157
PLoS One. 2013;8(1):e54448
pubmed: 23342160
ACS Chem Biol. 2017 Jul 21;12(7):1830-1841
pubmed: 28485919
Neurology. 1998 Dec;51(6):1546-54
pubmed: 9855500
J Mol Neurosci. 2011 Nov;45(3):538-48
pubmed: 21691802
Nucleic Acids Res. 2011 Nov 1;39(20):8677-88
pubmed: 21785136
J Histochem Cytochem. 2000 Jul;48(7):999-1009
pubmed: 10858277
BMC Biotechnol. 2004 Oct 15;4:23
pubmed: 15485583
Nat Med. 2003 Feb;9(2):225-9
pubmed: 12524533
J Mol Med (Berl). 2003 Oct;81(10):600-12
pubmed: 12928786
Neurobiol Aging. 2016 May;41:200.e1-200.e5
pubmed: 27021778
eNeuro. 2017 Aug 18;4(4):
pubmed: 28828399
Brain. 2006 Nov;129(Pt 11):3081-90
pubmed: 17071926
Brain. 2006 Nov;129(Pt 11):3091-102
pubmed: 17003069
PLoS One. 2014 May 07;9(5):e97032
pubmed: 24804730
Hum Mol Genet. 2017 Mar 1;26(5):969-988
pubmed: 28073925
FEBS J. 2018 Oct;285(19):3591-3603
pubmed: 29385658
J Biol Chem. 2003 Aug 22;278(34):31918-23
pubmed: 12813057
J Pept Res. 1999 May;53(5):590-7
pubmed: 10424355
Mol Neurodegener. 2017 Jul 25;12(1):55
pubmed: 28743268
PLoS One. 2013 May 31;8(5):e64989
pubmed: 23741441
Acta Neuropathol. 2014;127(6):845-60
pubmed: 24619111
Sci Transl Med. 2017 Apr 12;9(385):
pubmed: 28404863
Protein Sci. 2008 Apr;17(4):711-24
pubmed: 18359860
N Engl J Med. 2009 Oct 22;361(17):1651-61
pubmed: 19846850
J Exp Med. 2010 Jan 18;207(1):117-28
pubmed: 20026663
Biochemistry. 2000 Mar 21;39(11):2878-86
pubmed: 10715107
J Neurol. 2015;262(4):814-22
pubmed: 25578179
Nature. 1992 Jun 4;357(6377):407-10
pubmed: 1594045
Acta Neuropathol. 2017 Jul;134(1):151-153
pubmed: 28493053
Hum Mol Genet. 2017 Dec 15;26(24):4861-4872
pubmed: 29036611
Mol Neurodegener. 2017 Aug 23;12(1):62
pubmed: 28835281
Neurobiol Dis. 2008 Jul;31(1):41-5
pubmed: 18479928
Mol Genet Metab. 2012 Jul;106(3):257-63
pubmed: 22652185
Neuroscience. 2013 Feb 12;231:49-60
pubmed: 23201826
Biochim Biophys Acta. 1987 Sep 2;915(1):87-100
pubmed: 2956992
J Alzheimers Dis. 2014;38(4):747-52
pubmed: 24064467
Eur J Neurol. 2013 Dec;20(12):1571-3
pubmed: 23398167
J Proteomics. 2010 Jun 16;73(8):1479-90
pubmed: 20188224
EBioMedicine. 2016 Sep;11:127-137
pubmed: 27515686
Hum Mol Genet. 2006 Oct 15;15(20):2988-3001
pubmed: 16950801
Ann Neurol. 2006 Sep;60(3):314-22
pubmed: 16983685
Nat Rev Neurol. 2018 Jun;14(6):363-378
pubmed: 29777184
Nat Commun. 2017 May 25;8:15277
pubmed: 28541286
J Biol Chem. 2012 Sep 21;287(39):32298-306
pubmed: 22859297
J Biol Chem. 1992 Jun 25;267(18):13073-8
pubmed: 1618805
PLoS One. 2015 Aug 06;10(8):e0133749
pubmed: 26248158
Nat Struct Biol. 1996 Sep;3(9):747-52
pubmed: 8784346
Am J Hum Genet. 2012 Jun 8;90(6):1102-7
pubmed: 22608501
Nature. 2006 Aug 24;442(7105):916-9
pubmed: 16862116
Mol Med. 1994 Nov;1(1):82-92
pubmed: 8790604
EBioMedicine. 2016 Nov;13:212-224
pubmed: 27789271
Cell Rep. 2017 Sep 12;20(11):2565-2574
pubmed: 28903038
Hum Mol Genet. 2017 Aug 1;26(15):2850-2863
pubmed: 28453791
J Cell Biol. 2015 Sep 14;210(6):991-1002
pubmed: 26370502
Nature. 2006 Aug 24;442(7105):920-4
pubmed: 16862115
Proc Natl Acad Sci U S A. 1990 Oct;87(20):7912-6
pubmed: 2236009
Proc Natl Acad Sci U S A. 1989 May;86(9):3389-93
pubmed: 2717620
Science. 2013 Feb 15;339(6121):823-6
pubmed: 23287722
J Leukoc Biol. 2013 Feb;93(2):199-208
pubmed: 23089745
J Biol Chem. 1996 Mar 22;271(12):6874-80
pubmed: 8636113
Neuron. 2010 Nov 18;68(4):654-67
pubmed: 21092856
Nat Chem Biol. 2010 Dec;6(12):907-13
pubmed: 21079602
J Neurochem. 2017 Oct;143(2):236-243
pubmed: 28640985
Science. 2013 Feb 15;339(6121):819-23
pubmed: 23287718