著者

Masamitsu FUTAI Ge-Hong SUN-WADA Yoh WADA Naomi MATSUMOTO Mayumi NAKANISHI-MATSUI

出版者

The Japan Academy

雑誌

Proceedings of the Japan Academy, Series B (ISSN:03862208)

巻号頁・発行日

vol.95, no.6, pp.261-277, 2019-06-11 (Released:2019-06-11)

参考文献数

87

被引用文献数

74

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Vacuolar-type ATPase (V-ATPase), initially identified in yeast and plant vacuoles, pumps protons into the lumen of organelles coupled with ATP hydrolysis. The mammalian counterpart is found ubiquitously in endomembrane organelles and the plasma membrane of specialized cells such as osteoclasts. V-ATPase is also present in unique organelles such as insulin secretory granules, neural synaptic vesicles, and acrosomes of spermatozoa. Consistent with its diverse physiological roles and unique localization, the seven subunits of V-ATPase have 2–4 isoforms that are organelle- or cell-specific. Subunits of the enzyme function in trafficking organelles and vesicles by interacting with small molecule GTPases. During osteoclast differentiation, one of the four isoforms of subunit a, a3, is indispensable for secretory lysosome trafficking to the plasma membrane. Diseases such as osteopetrosis, renal acidosis, and hearing loss are related to V-ATPase isoforms. In addition to its role as an enzyme, V-ATPase has versatile physiological roles in eukaryotic cells.