Integrated physiology of proximal tubular organic anion transport.
OBJECTIVE
Renal organic anion transport proteins play important roles in the reabsorption and the secretion of endogenous and exogenous compounds. This review focuses on the interpretation of the physiological integration of identified transport molecules in the renal proximal tubules.


RESULTS
To date, molecular identification of organic anion transport proteins is still continuing: rodent organic anion transporter 5, organic anion-transporting polypeptide 4C1, voltage-driven organic anion transporter 1, multidrug resistance-associated protein 4, and sodium-coupled monocarboxylate transporter have yielded additional information in this field. In addition, particularly at the apical membrane of the proximal tubules, the importance of the PDZ (PSD-95, DglA, and ZO-1) binding domain proteins has emerged in the formation of the multimolecular complex as a functional unit of membrane transport. Finally, discovery of dicarboxylate receptors in the renal tubular cells raises the possibility that dicarboxylate anions function as intrarenal signaling molecules. This novel aspect of renal organic anion transport, the potential modulation of signaling via dicarboxylate receptors, may be of significant relevance to renovascular hypertension and other renal diseases.


CONCLUSIONS
Comprehensive understanding of the multimolecular complex, which is composed of transporters and their related signaling elements and is supported by the scaffold proteins underneath the plasma membrane, may be useful in clarifying complex transport phenomena such as renal apical organic anion handling. In addition to the recent proteomics approaches and conventional molecular physiology, it is necessary to develop novel methods to analyze the overall function of the multimolecular complex for the post-genomic era.
Anzai
Naohiko
N
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Tokyo 181-8611, Japan.
Jutabha
Promsuk
P
Kanai
Yoshikatsu
Y
Endou
Hitoshi
H
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008954:Models, Biological; D046912:Multiprotein Complexes; D027361:Organic Anion Transporters / Q000378:metabolism; D027701:Organic Cation Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D050608:Sodium-Phosphate Cotransporter Proteins / Q000378:metabolism
D002352:Carrier Proteins; D003998:Dicarboxylic Acids; D046912:Multiprotein Complexes; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C491241:SLC22A12 protein, human; D050608:Sodium-Phosphate Cotransporter Proteins; C078199:diazepam-binding inhibitor receptor