RRC ID 71572
Author Matsumoto N, Sekiya M, Sun-Wada GH, Wada Y, Nakanishi-Matsui M.
Title The lysosomal V-ATPase a3 subunit is involved in localization of Mon1-Ccz1, the GEF for Rab7, to secretory lysosomes in osteoclasts.
Journal Sci Rep
Abstract 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.
Volume 12(1)
Pages 8455
Published 2022-5-19
DOI 10.1038/s41598-022-12397-w
PII 10.1038/s41598-022-12397-w
PMID 35589873
PMC PMC9120031
MeSH Animals Endosomes / metabolism Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism HEK293 Cells Humans Lysosomes / metabolism Mice Osteoclasts / metabolism Protein Isoforms / genetics Protein Isoforms / metabolism Vacuolar Proton-Translocating ATPases* / genetics Vacuolar Proton-Translocating ATPases* / metabolism rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism
IF 3.998
Mice RBRC04421