Molecular chaperones in the kidney: distribution, putative roles, and regulation

Molecular chaperones are intracellular proteins that prevent inappropriate intra- and intermolecular interactions of polypetide chains. A specific gro up of highly conserved molecular chaperones are the heat shock proteins (HS Ps), many of which are constitutively expressed but most of which are induc ible by diverse (in some cases specific) stress factors. HSPs, either alone or in cooperation with "partner" chaperones, are involved in cellular proc esses as disparate as correct folding and assembly of proteins, transport o f proteins to specific intracellular locations, protein degradation, and pr eservation and restructuring of the cytoskeleton. The characteristic distri bution of individual HSPs in the kidney, and their response to different ch allenges, suggests that a number of HSPs may fulfill specific, kidney-relat ed functions. HSP72 and the osmotic stress protein 94 (Osp94) appear to par ticipate in the adaptation of medullary cells to high extracellular salt an d urea concentrations; the small HSPs (HSP25/27 and crystallins) may be inv olved in the function of mesangial cells and podocytes and contribute to th e volume-regulatory remodeling of the cytoskeleton in medullary cells durin g changes in extracellular tonicity. HSP90 contributes critically to the ma turation of steroid hormone receptors and may thus be a critical determinan t of the aldosterone sensitivity of specific renal epithelial cells. Certai n HSPs are also induced in various pathological states of the kidney. The o bservation that the expression of individual HSPs in specific kidney diseas es often displays characteristic time courses and intrarenal distribution p atterns supports the idea that HSPs are involved in the recovery but possib ly also in the initiation and/or maintenance phases of these disturbances.