Casuscelli J, Schmidt S, Degray B, Petri ET, Celic A, Folta-Stogniew E, Ehrlich BE, Boggon TJ
ANALYSIS OF THE CYTOPLASMIC INTERACTION BETWEEN POLYCYSTIN-1 AND POLYCYSTIN-2. [JOURNAL ARTICLE]
Am J Physiol Renal Physiol 2009 Sep 2.
Autosomal dominant polycystic kidney disease (ADPKD) arises following mutations of either Pkd1 or Pkd2. The proteins these genes encode, polycystin-1 (PC1) and polycystin-2 (PC2), form a signaling complex using direct intermolecular interactions. Two distinct domains in the C-terminal tail of PC2 have recently been identified, an EF-hand and a coiled coil domain. Here we show that the PC2 coiled coil domain interacts with the C-terminal tail of PC1, but that the PC2 EF-hand domain does not. We measure the K0.5 of the interaction between the C-terminal tails of PC1 and PC2 and show that the direct interaction of these proteins is abrogated by a PC1 point mutation that was identified in ADPKD patients. Finally, we show that overexpression of PC1 C-terminal tail in MDCK cells alters the calcium (Ca(2+)) response, but that overexpression of PC1 C-terminal tail containing the disease mutation does not. These results allow a more detailed understanding of the mechanism of pathogenic mutations in the cytoplasmic regions of PC1 and PC2. Key words: Polycystic kidney disease, Calcium signaling, Surface Plasmon Resonance, EF-hand.
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