Naslov
Novel aspects in regulated expression of the renal type IIa Na/Pi- cotransporter

Autori
Bačić, Deša ; Wagner, C.A. ; Hernando, N. ; Kaissling, B. ; Biber, J. ; Murer, H.

Izvornik
Kidney International Supplement (0085-2538) 66 (2004), S91; 5-12

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, osvrt, stručni

Ključne riječi
Proximal tubular phosphate reabsorption; regulated endocytosis; NaPi-IIa

Sažetak
Proximal tubular phosphate (P(i)) 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(P(i))-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 P(i)-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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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