Emerging roles of transporter-PDZ complexes in renal proximal tubular reabsorption

In the kidneys a large part of filtered solutes is reabsorbed by specific t ransporters localized in the microvilli of the proximal tubular cells (PT c ells). Depending on the body needs, the rates of reabsorption of certain so lutes are adjusted mostly by hormonal control mechanisms. Most transporters are distributed along the whole microvilli (approx. I Lm of length) and in the case of regulated transporters, they can also be detected in the inter microvillar clefts - the sites of internalization - associated with clathri n-coated pits/vesicles and in endosomal structures contained in the subapic al compartment. From the latter, internalized transporters may recycle back to the apical membrane or may be routed to the lysosomes. This arrangement of regulated and non-regulated transporters suggests that probably all tra nsporters interact in some way with other proteins. Such interactions are t hought to be involved in: (1) the targeting of transporters to the apical m embrane, (2) keeping microvillar transporters in place, (3) recruiting elem ents of the signalling cascades involved in regulating transport processes and (4) the processing of internalized transporters in the subapical compar tment. Very recently, we have begun to learn how supramolecular structures such as synapses are organized in terms of static and dynamic protein-protein inte ractions [3, 4, 13]. Proteins containing PDZ domains (name derived from the postsynaptic protein PSD95, dlg-A from Drosophila and the tight junction p rotein ZO-1) have emerged as important elements in organizing such membrane complexes. Several PDZ proteins have been identified that are expressed in epithelial cells and localized at the apical or the basolateral membrane. In this short commentary I shall restrict discussion to PDZ proteins locali zed in the brush borders of PT cells and speculate about their possible fun ctions regarding the sorting/positioning and regulation of solute transport ers.