Furin interacts with proMT 1 - MMP and integrin α V at specialized domains of renal cell plasma membrane

Synergistic interactions of cellular and extracellular elements are needed to establish and maintain multicellular organization and tissue-specific functions. A simple yet functionally complex example of such cooperation is encountered in the renal glomerulus. The glomerular wall, the highly specialized unit responsible for the selective ultrafiltration of the blood, is composed of three layers: a fenestrated endothelium, the glomerular basement membrane (GBM) and the filtration slits formed by the interdigitating foot processes of the visceral epithelial cells (podocytes). The slit diaphragm bridges the filtration slit to form specialized intercellular junctions (Kanwar and Venkatachalam, 1992). The structural integrity of the foot processes and their slit diaphragms with the appropriate turnover of the GBM components are key elements for the proper function of the glomerulus. A plethora of nephropathies are associated with podocyte-foot-process fusion and detachment, proteolytic degradation of the GBM, and extracellular matrix (ECM) accumulation, resulting in the loss of essential plasma proteins into the urinary space (Lenz et al., 2000; Barisoni and Kopp, 2002). Knowledge of the interactions among cell surface proteins mediating GBM turnover is crucial for an understanding of glomerulus function. Furin is a calcium-dependent serine protease of the subtilisin-like proprotein convertase family. This type I transmembrane glycoprotein is involved in pro-domain cleavage of many bioactive proteins traveling along the constitutive secretory route. It cleaves proteins at the C-terminal side of multibasic amino acid motifs such as R-X