Recent insights into the structure and functions of heparan sulfate proteoglycans in the human glomerular basement membrane

As the first barrier to be crossed on the way to urinary space, the glomeru lar basement membrane (GBM) plays a key role in renal function. The permeab ility of the GEM for a given molecule is highly dependent on its size, shap e and charge. As early as 1980, the charge-selective permeability was demon strated to relate to the electrostatic properties of covalently bound hepar an sulfates (HS) within the GEM. Since the identification of perlecan as a heparan sulfate proteoglycan (HSPG) of basement membranes, the hypothesis t hat perlecan could be a crucial determinant of GEM permselectivity received considerable attention. In addition to perlecan, the GEM also contains oth er HSPG species, one of which was identified as agrin. The high local expre ssion of agrin in the GEM, together with the presence of agrin receptors at the cell-matrix interface, suggests that this HSPG contributes to glomerul ar function in multiple ways. Here, we review the current knowledge regardi ng the structure and functions of HSPGs in the GEM, and discuss how these m olecules could be involved in various glomerular diseases. Possible directi ons for future investigation are suggested.