Co-assembly of polycystin-1 and-2 produces unique cation-permeable currents

K Hanaoka, F Qian, A Boletta, AK Bhunia, K Piontek… - Nature, 2000 - nature.com
K Hanaoka, F Qian, A Boletta, AK Bhunia, K Piontek, L Tsiokas, VP Sukhatme, WB Guggino
Nature, 2000nature.com
The human kidney is composed of roughly 1.2-million renal tubules that must maintain their
tubular structure to function properly. In autosomal dominant polycystic kidney disease
(ADPKD) cysts develop from renal tubules and enlarge independently, in a process that
ultimately causes renal failure in 50% of affected individuals,. Mutations in either PKD1 or
PKD2 are associated with ADPKD but the function of these genes is unknown. PKD1 is
thought to encode a membrane protein, polycystin-1, involved in cell–cell or cell–matrix …
Abstract
The human kidney is composed of roughly 1.2-million renal tubules that must maintain their tubular structure to function properly. In autosomal dominant polycystic kidney disease (ADPKD) cysts develop from renal tubules and enlarge independently, in a process that ultimately causes renal failure in 50% of affected individuals,. Mutations in either PKD1 or PKD2 are associated with ADPKD but the function of these genes is unknown. PKD1 is thought to encode a membrane protein, polycystin-1, involved in cell–cell or cell–matrix interactions,,, whereas the PKD2 gene product, polycystin-2, is thought to be a channel protein. Here we show that polycystin-1 and -2 interact to produce new calcium-permeable non-selective cation currents. Neither polycystin-1 nor -2 alone is capable of producing currents. Moreover, disease-associated mutant forms of either polycystin protein that are incapable of heterodimerization do not result in new channel activity. We also show that polycystin-2 is localized in the cell in the absence of polycystin-1, but is translocated to the plasma membrane in its presence. Thus, polycystin-1 and -2 co-assemble at the plasma membrane to produce a new channel and to regulate renal tubular morphology and function.
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