Vacuolar-type ATPase: A proton pump to lysosomal trafficking

Futai, Masamitsu; Sun‐Wada, Ge‐Hong; Wada, Yoh; Matsumoto, Naomi; Nakanishi‐Matsui, Mayumi

doi:10.2183/pjab.95.018

Cited by 85 publications

(82 citation statements)

References 87 publications

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“…An acidic pH is important for many physiological processes, such as renal acidification, bone resorption, and sperm maturation. V-ATPases localize to the plasma membrane, endosomes, and membrane vesicles and play an important role in proton homeostasis 1 – 4 . V-ATPase is involved in autophagy 5 , metabolism 6 , 7 , and neurotransmitter secretion 3 .…”

Section: Introductionmentioning

confidence: 99%

Cryo-EM structures of intact V-ATPase from bovine brain

et al. 2020

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The vacuolar-type H +-ATPases (V-ATPase) hydrolyze ATP to pump protons across the plasma or intracellular membrane, secreting acids to the lumen or acidifying intracellular compartments. It has been implicated in tumor metastasis, renal tubular acidosis, and osteoporosis. Here, we report two cryo-EM structures of the intact V-ATPase from bovine brain with all the subunits including the subunit H, which is essential for ATPase activity. Two type-I transmembrane proteins, Ac45 and (pro)renin receptor, along with subunit c", constitute the core of the c-ring. Three different conformations of A/B heterodimers suggest a mechanism for ATP hydrolysis that triggers a rotation of subunits DF, inducing spinning of subunit d with respect to the entire c-ring. Moreover, many lipid molecules have been observed in the Vo domain to mediate the interactions between subunit c, c", (pro)renin receptor, and Ac45. These two structures reveal unique features of mammalian V-ATPase and suggest a mechanism of V1-Vo torque transmission.

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Section: Introductionmentioning

confidence: 99%

Cryo-EM structures of intact V-ATPase from bovine brain

et al. 2020

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“…Furthermore, nutrients and growth factors can drive lysosomes toward the plasma membrane, whereas starvation results in lysosomes moving toward perinuclear localization [46,47]. Vacuolar-type proton pumping ATPase (V-ATPase) is a ubiquitous enzyme responsible for H + transport across membranes and acidification of cellular compartments in animals [48]. The phosphate bond energy of ATP is thus converted to a proton gradient across the membrane through the mechanical rotation of subunits.…”

Section: Autophagic Fluxmentioning

confidence: 99%

“…The phosphate bond energy of ATP is thus converted to a proton gradient across the membrane through the mechanical rotation of subunits. The proton pumping action of lysosomal V-ATPases results in the generations of an acidic lumen and proton gradient of lysosomes, which are essential for normal functions of lysosomes [48]. A recent study in our lab has revealed that inhibition of V-ATPase activity remarkably attenuated lysosome function, leading to autophagic deficiency and podocyte dedifferentiation [26].…”

Section: Autophagic Fluxmentioning

confidence: 99%

Podocyte Lysosome Dysfunction in Chronic Glomerular Diseases

Kidd

2020

IJMS

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Podocytes are visceral epithelial cells covering the outer surface of glomerular capillaries in the kidney. Blood is filtered through the slit diaphragm of podocytes to form urine. The functional and structural integrity of podocytes is essential for the normal function of the kidney. As a membrane-bound organelle, lysosomes are responsible for the degradation of molecules via hydrolytic enzymes. In addition to its degradative properties, recent studies have revealed that lysosomes may serve as a platform mediating cellular signaling in different types of cells. In the last decade, increasing evidence has revealed that the normal function of the lysosome is important for the maintenance of podocyte homeostasis. Podocytes have no ability to proliferate under most pathological conditions; therefore, lysosome-dependent autophagic flux is critical for podocyte survival. In addition, new insights into the pathogenic role of lysosome and associated signaling in podocyte injury and chronic kidney disease have recently emerged. Targeting lysosomal functions or signaling pathways are considered potential therapeutic strategies for some chronic glomerular diseases. This review briefly summarizes current evidence demonstrating the regulation of lysosomal function and signaling mechanisms as well as the canonical and noncanonical roles of podocyte lysosome dysfunction in the development of chronic glomerular diseases and associated therapeutic strategies.

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“…Also, the fact that the annotations for SPERM did not contain specificities is unsurprising: After all, many sperm-expressed proteins exert their multiple functions in diverse tissues [Schumacher and Herlyn, 2018]. Nevertheless, SPERM also exhibited clear connections to re-production, as exemplified by TSG10 (TSGA10), which is mainly expressed in sperm tail, and VATE2 (ATP6V1E2; alias VMA4), which participates in acrosomal acidification [Sha et al, 2018;Futai et al, 2019]. However, most such associations existed for the protein set representing the organ of spermiogenesis, TESTIS.…”

Section: General Characteristics Of Protein Sets and Testis Specialtiesmentioning

confidence: 99%

Intra-Protein Coevolution Is Increasingly Functional with Greater Proximity to Fertilization

Kwiatkowski

Asif

Schumacher

et al. 2020

Cytogenet Genome Res

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Intramolecular coevolution of amino acid sites has repeatedly been studied to improve predictions on protein structure and function. Thereby, the focus was on bacterial proteins with available crystallographic data. However, intramolecular coevolution has not yet been compared between protein sets along a gradient of functional proximity to fertilization. This is especially true for the potential effect of external selective forces on intraprotein coevolution. In this study, we investigated both aspects in equally sized sets of mammalian proteins representing spermatozoa, testis, entire body, and liver. For coevolutionary analyses, we derived the proportion of covarying sites per protein from amino acid alignments of 10 mammalian orthologues each. In confirmation of the validity of our coevolution proxy, we found positive associations with the nonsynonymous or amino acid substitution rate in all protein sets. However, our coevolution proxy negatively correlated with the number of protein interactants (node degree) in male reproductive protein

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Vacuolar-type ATPase: A proton pump to lysosomal trafficking

Cited by 85 publications

References 87 publications

Cryo-EM structures of intact V-ATPase from bovine brain

Cryo-EM structures of intact V-ATPase from bovine brain

Podocyte Lysosome Dysfunction in Chronic Glomerular Diseases

Intra-Protein Coevolution Is Increasingly Functional with Greater Proximity to Fertilization

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