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ICHIHARA Atsuhiro
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Professor and Division head |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | The role of individual domains and the significance of shedding of ATP6AP2/(pro)renin receptor in vacuolar H(+)-ATPase biogenesis. |
| Journal | Formal name：PloS one Abbreviation：PLoS One ISSN code：1932-6203(Electronic)1932-6203(Linking) |
| Volume, Issue, Page | 8(11),pp.e78603 |
| Author and coauthor | KINOUCHI Kenichiro†, ICHIHARA Atsuhiro*, SANO Motoaki, SUN-WADA Ge-Hong, WADA Yoh, OCHI Hiroki, FUKUDA Toru, BOKUDA Kanako, KUROSAWA Hideaki, YOSHIDA Naohiro, TAKEDA Shu, FUKUDA Keiichi, ITOH Hiroshi |
| Authorship | Corresponding author |
| Publication date | 2013/02 |
| Summary | The ATPase 6 accessory protein 2 (ATP6AP2)/(pro)renin receptor (PRR) is essential for the biogenesis of active vacuolar H(+)-ATPase (V-ATPase). Genetic deletion of ATP6AP2/PRR causes V-ATPase dysfunction and compromises vesicular acidification. Here, we characterized the domains of ATP6AP2/PRR involved in active V-ATPase biogenesis. Three forms of ATP6AP2/PRR were found intracellularly: full-length protein and the N- and C-terminal fragments of furin cleavage products, with the N-terminal fragment secreted extracellularly. Genetic deletion of ATP6AP2/PRR did not affect the protein stability of V-ATPase subunits. The extracellular domain (ECD) and transmembrane domain (TM) of ATP6AP2/PRR were indispensable for the biogenesis of active V-ATPase. A deletion mutant of ATP6AP2/PRR, which lacks exon 4-encoded amino acids inside the ECD (Δ4M) and causes X-linked mental retardation Hedera type (MRXSH) and X-linked parkinsonism with spasticity (XPDS) in humans, was defective as a V-ATPase-associated protein. Prorenin had no effect on the biogenesis of active V-ATPase. The cleavage of ATP6AP2/PRR by furin seemed also dispensable for the biogenesis of active V-ATPase. We conclude that the N-terminal ECD of ATP6AP2/PRR, which is also involved in binding to prorenin or renin, is required for the biogenesis of active V-ATPase. The V-ATPase assembly occurs prior to its delivery to the trans-Golgi network and hence shedding of ATP6AP2/PRR would not affect the biogenesis of active V-ATPase. |
| DOI | 10.1371/journal.pone.0078603 |
| Document No. | 24223829 |