Identification of a Polycystin-1 Cleavage Product, P100, That Regulates Store Operated Ca2+ Entry through Interactions with STIM1

• DOI: 10.1371/journal.pone.0012305
• Publication Date: 2010-08-23T20:44:41Z
• Authors: Owen M. Woodward; Yun Li; Shengqiang Yu; Patrick Greenwell; Claas Wodarczyk; Alessandra Boletta; William B. Guggino; Feng Qian
• Keywords: PKD1; Orai1; Cleavage (geology); HEK 293 cells; Thapsigargin

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder resulting in large kidney cysts and eventual failure. Mutations either the PKD1 or PKD2/TRPP2 genes their respective protein products, polycystin-1 (PC1) polycystin-2 (PC2) result ADPKD. PC2 known to function as non-selective cation channel, but PC1's of PC1 cleavage products are not well understood. Here we identify an endogenous product, P100, 100 kDa fragment found both wild type epitope tagged knock-in mice. Expression full length human (FL PC1) P100 C-Terminal Fragment (CTF) MDCK CHO cells significantly reduces store operated Ca2+ entry (SOCE) from thapsigargin induced depletion. Exploration into roles CTF SOCE inhibition reveal that when expressed Xenopus laevis oocytes, directly inhibits currents does not, nor containing disease causing R4227X mutation. Interestingly, also expressing cells, translocation ER sensor STIM1 cell periphery was altered. In addition, Co-immunoprecipitates with not. The expression recapitulates seen FL PC1. These data describe novel which functions reduce via direct translocation; consequences for