Luminal acidification in the epididymis is an important process for the regulation of male fertility. Low pH and low bicarbonate concentration are among key factors that keep spermatozoa in a dormant state while they mature and are stored in this organ. Although significant bicarbonate reabsorption is achieved by principal cells in the proximal regions of the epididymis, clear and narrow cells are specialized for net proton secretion. Clear cells express very high levels of the vacuolar proton pumping ATPase (V-ATPase) in their apical membrane and are responsible for the bulk of proton secretion. In the present paper, selected aspects of V-ATPase regulation in clear cells are described and potential pathologies associated with mutations of some of the V-ATPase subunits are discussed.
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Int J Biol Macromol
January 2025
Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address:
Proanthocyanidins (PAs) are the second most abundant plant phenolic natural products. The proton membrane H-ATPase (AHA) is required for PA transportation in vacuoles, but it remains unclear which AHA gene(s) encode tonoplast proton pump in M. truncatula.
View Article and Find Full Text PDFiScience
January 2025
Department of Experimental Medicine, University of Genova, Viale Benedetto XV/3, 16132 Genoa, Italy.
The vacuolar ATPase (v-ATPase) is essential for acidification of intracellular organelles, including synaptic vesicles. Its activity is controlled by cycles of association and dissociation of the ATP hydrolysis (V) and proton transport (V) multi-protein subunits. Mutations in genes coding for both v-ATPase subunits and TBC1D24 cause neurodevelopmental disorders with overlapping syndromes; therefore, it is important to investigate their potentially interrelated functions.
View Article and Find Full Text PDFAutophagy
January 2025
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
The vacuolar-type H-ATPase (V-ATPase) is a proton pump responsible for controlling the intracellular and extracellular pH of cells. Its activity and assembly are tightly controlled by multiple pathways, of which phosphorylation-mediated regulation is poorly understood. In this report, we show that in response to starvation stimuli, the nonreceptor tyrosine kinase ABL1 directly interacts with ATP6V1B2, a subunit of the V domain of the V-ATPase, and phosphorylates ATP6V1B2 at Y68.
View Article and Find Full Text PDFNat Commun
January 2025
School of Infection and Immunity, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow, G12 8TA, UK.
For the protozoan parasite Leishmania, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the L.
View Article and Find Full Text PDFJ Cell Physiol
January 2025
Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Megalin is a multiple-ligand receptor that contributes to protein reabsorption in the kidney. Recently, megalin was found to act as a novel endocytic receptor for prorenin. Internalization depended on the (pro)renin receptor.
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