Regulation of the V-ATPase in kidney epithelial cells: dual role in acid–base homeostasis and vesicle trafficking

Abstract

SummaryThe proton-pumping V-ATPase is a complex, multi-subunit enzyme that is highly expressed in the plasma membranes of some epithelial cells in the kidney, including collecting duct intercalated cells. It is also located on the limiting membranes of intracellular organelles in the degradative and secretory pathways of all cells. Different isoforms of some V-ATPase subunits are involved in the targeting of the proton pump to its various intracellular locations, where it functions in transporting protons out of the cell across the plasma membrane or acidifying intracellular compartments. The former process plays a critical role in proton secretion by the kidney and regulates systemic acid-base status whereas the latter process is central to intracellular vesicle trafficking, membrane recycling and the degradative pathway in cells. We will focus our discussion on two cell types in the kidney: (1) intercalated cells, in which proton secretion is controlled by shuttling V-ATPase complexes back and forth between the plasma membrane and highly-specialized intracellular vesicles, and (2) proximal tubule cells, in which the endocytotic pathway that retrieves proteins from the glomerular ultrafiltrate requires V-ATPase-dependent acidification of post-endocytotic vesicles. The regulation of both of these activities depends upon the ability of cells to monitor the pH and/or bicarbonate content of their extracellular environment and intracellular compartments. Recent information about these pH-sensing mechanisms, which include the role of the V-ATPase itself as a pH sensor and the soluble adenylyl cyclase as a bicarbonate sensor, will be addressed in this review.

Activity of Plasma Membrane V-ATPases Is Critical for the Invasion of MDA-MB231 Breast Cancer Cells

“…The vacuolar (H ϩ )-ATPases (V-ATPases) 4 are ubiquitously expressed, ATP-dependent proton pumps present in lysosomes, endosomes, secretory vesicles, clathrin-coated vesicles, and the plasma membranes of certain specialized cell types (7)(8)(9). The primary role of the V-ATPase is to pump protons from the cytosol into intracellular compartments or the extracellular space.…”

Archazolid A-15-O-β-d-glucopyranoside and iso-Archazolid B: Potent V-ATPase Inhibitory Polyketides from the Myxobacteria Cystobacter violaceus and Archangium gephyra

“…5 Furthermore, plasma membrane V-ATPases have critical functions in different physiological processes such as urinary acidification, 6,7 bone resorption, 8 and sperm maturation. 9 V-ATPases are associated with various human diseases, including osteoporosis, tubular acidosis, tumor metastasis, infection by influenza and other viruses, and bacterial infections by anthrax or diphtheria 10 and have an increasingly emerging potential as drug targets.…”

Proteomic changes in response to crystal formation inDrosophilaMalpighian tubules

“…17,18 These range from proton secretion in order to acidify the extracellular milieu, to intracellular acidification of vesicles and regulation of a variety of processes that range from lysosomal degradation, ligand receptor dissociation and intracellular trafficking. 19 The holoenzyme is comprised of many different subunits, each having different functions that are involved not only in the activity of the enzyme but also to its intracellular regulation and targeting. It might be an important agent in the common pathways in kidney crystal pathogenesis as several other V-ATPase subunits has been identified in the Progenesis analysis as well.…”