The lysosomal V-ATPase a3 subunit is involved in localization of Mon1-Ccz1, the GEF for Rab7, to secretory lysosomes in osteoclasts.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 05 2022
19 05 2022
Historique:
received:
11
12
2021
accepted:
10
05
2022
entrez:
19
5
2022
pubmed:
20
5
2022
medline:
24
5
2022
Statut:
epublish
Résumé
We have shown previously that the lysosomal a3 isoform of the a subunit of vacuolar-type ATPase (V-ATPase) interacts with inactive (GDP-bound form) Rab7, a small GTPase that regulates late endosome/lysosome trafficking, and that a3 recruits Rab7 to secretory lysosomes in mouse osteoclasts. This is essential for outward trafficking of secretory lysosomes and thus for bone resorption. However, the molecular mechanism underlying the recruitment of Rab7 by a3 remains to be fully elucidated. Here, we showed that a3 interacts with the Mon1A-Ccz1 complex, a guanine nucleotide exchange factor (GEF) for Rab7, using HEK293T cells. The interaction was mediated by the amino-terminal half domain of a3 and the longin motifs of Mon1A and Ccz1. Exogenous expression of the GEF promoted the interaction between a3 and Rab7. Mon1A mutants that interact inefficiently with Rab7 interacted with a3 at a similar level to wild-type Mon1A. Lysosomal localization of endogenous Ccz1 was abolished in osteoclasts lacking a3. These results suggest that the lysosomal a3 isoform of V-ATPase interacts with Mon1A-Ccz1, and that a3 is important for Mon1A-Ccz1 localization to secretory lysosomes, which mediates Rab7 recruitment to the organelle.
Identifiants
pubmed: 35589873
doi: 10.1038/s41598-022-12397-w
pii: 10.1038/s41598-022-12397-w
pmc: PMC9120031
doi:
Substances chimiques
Guanine Nucleotide Exchange Factors
0
Protein Isoforms
0
Vacuolar Proton-Translocating ATPases
EC 3.6.1.-
rab GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8455Informations de copyright
© 2022. The Author(s).
Références
Int J Mol Sci. 2021 Jun 28;22(13):
pubmed: 34203247
J Biol Chem. 2013 Oct 4;288(40):28704-12
pubmed: 23979137
J Cell Sci. 2016 Dec 1;129(23):4329-4339
pubmed: 27799357
Traffic. 2012 Oct;13(10):1307-14
pubmed: 22759194
Physiology (Bethesda). 2013 Sep;28(5):318-29
pubmed: 23997191
Biochemistry. 2010 Jun 15;49(23):4715-23
pubmed: 20450191
J Cell Sci. 2016 Jan 15;129(2):329-40
pubmed: 26627821
Cell Struct Funct. 2016 Jul 9;41(2):61-79
pubmed: 27246931
Science. 2004 Jul 2;305(5680):55-9
pubmed: 15232098
J Biol Chem. 2001 Oct 19;276(42):39295-302
pubmed: 11514537
Nat Cell Biol. 2006 Feb;8(2):124-36
pubmed: 16415858
Sci Rep. 2018 Apr 30;8(1):6701
pubmed: 29712939
Small GTPases. 2018 Mar 4;9(1-2):5-21
pubmed: 28055292
Nat Commun. 2017 Jan 04;8:14034
pubmed: 28051187
Exp Cell Res. 2014 Oct 15;328(1):1-19
pubmed: 25088255
Front Cell Dev Biol. 2020 Jun 23;8:510
pubmed: 32656214
Curr Biol. 2010 Sep 28;20(18):1654-9
pubmed: 20797862
Annu Rev Genomics Hum Genet. 2008;9:359-86
pubmed: 18544035
J Cell Sci. 2015 Dec 1;128(23):4263-72
pubmed: 26567219
Exp Cell Res. 2020 Apr 15;389(2):111901
pubmed: 32045577
Biosci Rep. 2009 Jun;29(3):193-209
pubmed: 19392663
Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(6):261-277
pubmed: 31189779
Mod Rheumatol. 2012 Apr;22(2):167-77
pubmed: 21953286
Front Cell Dev Biol. 2018 Oct 02;6:129
pubmed: 30333976
Cells. 2016 Aug 18;5(3):
pubmed: 27548222
Small GTPases. 2014;5(3):1-3
pubmed: 25483304
Cold Spring Harb Perspect Biol. 2014 Sep 02;6(9):a016840
pubmed: 25183830
Curr Opin Cell Biol. 2008 Aug;20(4):415-26
pubmed: 18511251
J Cell Sci. 2014 Mar 1;127(Pt 5):1043-51
pubmed: 24413168
Curr Opin Cell Biol. 2013 Aug;25(4):414-9
pubmed: 23639309
Biomed Res Int. 2018 Aug 15;2018:4541538
pubmed: 30186859
J Cell Sci. 2015 Sep 1;128(17):3171-6
pubmed: 26272922
Bone Res. 2013 Mar 29;1(1):11-26
pubmed: 26273491
Biochim Biophys Acta. 2014 Jun;1837(6):744-9
pubmed: 24561225
Curr Opin Cell Biol. 2010 Aug;22(4):461-70
pubmed: 20466531