Polycystin 1

Protein structure and function

PC1 is a membrane-bound protein 4303 amino acids in length expressed largely upon the primary cilium, as well as apical membranes, adherens junctions, and desmosomes. It has 11 transmembrane domains, a large extracellular N-terminal domain, and a short (about 200 amino acid) cytoplasmic C-terminal domain. This intracellular domain contains a coiled-coil domain through which PC1 interacts with polycystin 2 (PC2), a membrane-bound Ca2+-permeable ion channel.

PC1 has been proposed to act as a G protein–coupled receptor. The C-terminal domain may be cleaved in a number of different ways. In one instance, a ~35 kDa portion of the tail has been found to accumulate in the cell nucleus in response to decreased fluid flow in the mouse kidney. In another instance, a 15 kDa fragment may be yielded, interacting with transcriptional activator and co-activator STAT6 and p100, or components of the canonical Wnt signaling pathway in an inhibitory manner.

The structure of the human PKD1-PKD2 complex has been solved by cryo-electron microscopy, which showed a 1:3 ratio of PKD1 and PKD2 in the structure. PKD1 consists of a voltage-gated ion channel fold that interacts with PKD2.

PC1 mediates mechanosensation of fluid flow by the primary cilium in the renal epithelium and of mechanical deformation of articular cartilage.

Gene

Splice variants encoding different isoforms have been noted for PKD1. The gene is closely linked to six pseudogenes in a known duplicated region on chromosome 16p.

References

References

1. (June 1995). "The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains". Nature Genetics.
2. (April 1995). "Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium". Cell.
3. (April 2007). "Autosomal dominant polycystic kidney disease". Lancet.
4. (2009). "Polycystins and primary cilia: primers for cell cycle progression". Annual Review of Physiology.
5. (October 2010). "Polycystin-1: function as a mechanosensor". The International Journal of Biochemistry & Cell Biology.
6. (January 2016). "The Role of G-Protein-Coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kidney Disease". Cells.
7. (November 2004). "Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus". The Journal of Clinical Investigation.
8. (January 2006). "Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease". Developmental Cell.
9. (October 2008). "Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical Wnt signaling". Human Molecular Genetics.
10. (2018-09-07). "Structure of the human PKD1-PKD2 complex". Science.
11. (February 2003). "Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells". Nature Genetics.
12. "Entrez Gene: PKD1 polycystic kidney disease 1 (autosomal dominant)".