Polycystins: What polycystic kidney disease tells us about sperm

Experimental evidence indicates that. the membrane-associated: proteins polycystin-1 and polycystin-2 operate as a receptor-calcium channel complex that regulates signaling pathways, essential for modulation of renal. tubulogenesis. Polycystic kidney disease is characterized by defective renal tubular structure and results from: mutations in either PKD1 or PKD2 genes. Recent data suggest that. polycystin-1 and polycystin-2 might localize to primary cilium in principal. cells of. renal! collecting: tubules, and are thought to act as mechanosensors of fluid, flow and contents. Ciliary bending by fluid flow or mechanical stimulation induce Ca2+ release from: intracellular stores, presumably to modulate ions influx in response to tubular fluid. flow. Polycystins are also emerging as playing a significant role in sperm development and function., Drosophila polycystin-2 is associated! with the head and tail of mature sperm. Targeted disruption, of the PKD2 homolog results in, nearly complete: male sterility without disrupting spermatogenesis, Mutant sperm are motile but are unable to reach the female storage organs (seminal receptacles and; spermathecae). The sea, urchin polycystin-l-equivalent suPC2 colocalizes with the polycystin-1 homolog REJ3 to, the plasma: membrane over the acrosomal vesicle . This localization. site suggests that, the suPC2-REJ3 complex may function. as a cation channel mediating acrosome reaction when sperm contact the jelly layer surrounding, the egg at fertilization, Future studies, leading to the identification of specific ligands for polycystins, including the signaling pathways, might define the puzzling relationship, between, renal tubular morphogenesis and sperm development and function. (C) 2004 Wiley-Liss, Inc.