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- Title
Novel aspects in regulated expression of the renal type IIa Na/P<sub>i</sub>-cotransporter.
- Authors
Bacic, Desa; Wagner, Carsten A.; Hernando, Nati; Kaissling, Brigitte; Biber, Jürg; Murer, Heini
- Abstract
Novel aspects in regulated expression of the renal type IIa Na/Pi-cotransporter. Proximal tubular phosphate (Pi) reabsorption is a key element in overall phosphate homeostasis; physiologic/pathophysiologic alterations are related to the control of brush border membrane expression (regulated endocytosis) of the type IIa sodium (Na)/phosphate(Pi)-cotransporter (NaPi-IIa). The carboxy terminus of NaPi-IIa contains sequences important for its apical delivery/expression; the last three amino acids are involved in PSD95/DglA/ZO-1 (PDZ) interactions involving NaPi-IIa, Na/H exchanger-regulatory factor 1 (NHERF1/2), and PDZK1/2 (apical scaffold). Regulated endocytosis of NaPi-IIa[e.g., parathyroid hormone (PTH)-induced] is reduced in megalin-deficient mice; internalization occurs via clathrin-coated structures, early endosomes, and finally leads to lysosomal degradation. NaPi-IIa contains, in the third intracellular loop, a sequence motif required for internalization. Different hormonal[e.g., PTH, atrial natriuretic peptide (ANP), also nitric oxide (NO)] and nonhormonal factors activate a variety of intracellular signaling cascades[protein kinase A (PK-A), protein kinase C (PK-C), protein kinase G (PK-G), extracellular receptor kinase (ERK)-1/2] leading (by unknown mechanisms) to NaPi-IIa internalization. Different phosphatonins[e.g., fibroblast growth factor (FGF)-23, frizzled related protein (FRP)-4, matrix extracellularphosphoglycoprotein (MEPE)], associated with different pathophysiologic states of renal Pi–handling, seem also to control apical expression of NaPi-IIa. Internalization of NaPi-IIa first requires its removal from the apical scaffold. This scaffold can also be considered as a regulatory scaffold containing also protein kinase A (PK-A)–anchoring proteins (AKAPs, ezrin) and the apical PTH receptor. The role of the different components of the regulatory scaffold in regulated endocytosis of NaPi-IIa is at present unknown.
- Subjects
SODIUM phosphates; PHOSPHATES; ENDOCYTOSIS; ABSORPTION (Physiology); KIDNEY physiology; CELL physiology; HOMEOSTASIS
- Publication
Kidney International Supplement, 2004, Issue 91, pS5
- ISSN
0098-6577
- Publication type
Article
- DOI
10.1111/j.1523-1755.2004.09102.x