Functional complementation of V-ATPase a subunit isoforms in osteoclasts. (2nd November 2020)

• Record Type: Journal Article
• Authors: Matsumoto, Naomi; Sekiya, Mizuki; Fujimoto, Yasuyuki; Haga, Satoshi; Sun-Wada, Ge-Hong; Wada, Yoh; Nakanishi-Matsui, Mayumi
• Is Part Of: Journal of biochemistry. Volume 169:Number 4(2021)
• Page Start: 459
• Page End: 466
• Publication Date: 2020-11-02
• Subjects: a subunit isoform -- osteoclast -- Rab7 -- secretory lysosome -- V-ATPase; Biochemistry -- Periodicals; Biochemistry -- Periodicals; Electronic journals; 572.05
• DOI: 10.1093/jb/mvaa118
• Languages: English
• ISSNs: 0021-924X

Abstract

Abstract: In osteoclasts, the a 3 isoform of the proton-pumping V-ATPase plays essential roles in anterograde trafficking of secretory lysosomes and extracellular acidification required for bone resorption. This study examined functional complementation of the a isoforms by exogenously expressing the a 1, a 2 and a 3 isoforms in a 3-knockout (KO) osteoclasts. The expression levels of a 1 and a 2 in a 3KO osteoclasts were similar, but lower than that of a 3. a 1 significantly localized to lysosomes, whereas a 2 slightly did. On the other hand, a 2 interacted with Rab7, a regulator of secretory lysosome trafficking in osteoclasts, more efficiently than a 1. a 1 partly complemented the functions of a 3 in secretory lysosome trafficking and calcium phosphate resorption, while a 2 partly complemented the former but not the latter function. Graphical Abstract: