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Polycystins and Autosomal Polycystic Kidney Disease

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Animal Lectins: Form, Function and Clinical Applications

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Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenic disorders, and globally is the third most common cause of end-stage kidney disease. Approximately 85% of ADPKD cases are attributable to mutations in polycystic kidney disease (PKD) gene 1 (PKD1) on chromosome 16, while mutations in PKD2 gene on chromosome 4 account for almost all of the remaining cases. These two diseases are phenotypically almost identical, differing only by the higher age of diagnosis with PKD2, and its slower progression to end-stage renal disease. The product of PKD1, polycystin-1 (PC-1), is a very large protein (4,303 amino acids), and is a membrane glycoprotein widely expressed in epithelial cells. It is also expressed in tight junctions, adherens junctions, desmosomes, apical junctions and primary cilia. Polycystin-2 (PC-2), the product of PKD2, is a smaller protein (968 amino acids) mainly present in the endoplasmic reticulum, but also in the cell plasma membrane. PC-1 and -2 are joined via a domain in the carboxy-tail of PC-1, and appear to act in concert (Ong and Harris 2005). PC-2 acts as a Ca2+ channel. It appears that PKD1 and PKD2 associate physically in vivo and may be partners of a common signaling cascade involved in tubular morphogenesis (Qian et al. 1997). Qian et al. (1997) defined naturally occurring pathogenic mutations of PKD1 and PKD2 that disrupt their associations. Portions of the cellular populations of PC-1 and PC-2 localize to the primary cilium. The ADPKD is the founding member of the “ciliopathies,” a recently defined class of genetic disorders that result from mutations in genes encoding cilia-associated proteins.

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  1. Department of Biophysics, Punjab University, Chandigarh, India

    G. S. Gupta (Former Professor and Chairman)

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Gupta, G.S. (2012). Polycystins and Autosomal Polycystic Kidney Disease. In: Animal Lectins: Form, Function and Clinical Applications. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1065-2_45

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