From Wikipedia, the free encyclopedia
Family of transport proteins
Polycystin 1 (PC1 ) is a
protein that in
humans is encoded by the PKD1
gene .
[5]
[6] Mutations of PKD1 are associated with most cases of
autosomal dominant polycystic kidney disease , a severe
hereditary disorder of the
kidneys characterised by the development of renal cysts and severe kidney dysfunction.
[7]
Protein structure and function
PC1 interacts with
polycystin 2 by a cytoplasmic coiled-coil domain.
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 .
[8] It has 11
transmembrane domains , a large extracellular N-terminal domain, and a short (about 200 amino acid)
cytoplasmic C-terminal domain.
[8]
[9] 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 .
[8]
[10] 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.
[11] 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.
[12]
[13]
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.
[14]
PC1 mediates
mechanosensation of fluid flow by the primary cilium in the renal epithelium and of mechanical deformation of
articular cartilage .
[15]
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.
[16]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000008710 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000032855 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millán JL, Gamble V, Harris PC (June 1995). "The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains". Nature Genetics . 10 (2): 151–60.
doi :
10.1038/ng0695-151 .
PMID
7663510 .
S2CID
20636101 .
^
"Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium" . Cell . 81 (2): 289–98. April 1995.
doi :
10.1016/0092-8674(95)90339-9 .
PMID
7736581 .
S2CID
11114706 .
^ Torres VE, Harris PC, Pirson Y (April 2007). "Autosomal dominant polycystic kidney disease". Lancet . 369 (9569): 1287–301.
doi :
10.1016/S0140-6736(07)60601-1 .
PMID
17434405 .
S2CID
1700992 .
^
a
b
c Zhou J (2009). "Polycystins and primary cilia: primers for cell cycle progression". Annual Review of Physiology . 71 : 83–113.
doi :
10.1146/annurev.physiol.70.113006.100621 .
PMID
19572811 .
^ Dalagiorgou G, Basdra EK, Papavassiliou AG (October 2010). "Polycystin-1: function as a mechanosensor". The International Journal of Biochemistry & Cell Biology . 42 (10): 1610–3.
doi :
10.1016/j.biocel.2010.06.017 .
PMID
20601082 .
^ Trudel M, Yao Q, Qian F (January 2016).
"The Role of G-Protein-Coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kidney Disease" . Cells . 5 (1): 3.
doi :
10.3390/cells5010003 .
PMC
4810088 .
PMID
26805887 .
^ Chauvet V, Tian X, Husson H, Grimm DH, Wang T, Hiesberger T, Hieseberger T, Igarashi P, Bennett AM, Ibraghimov-Beskrovnaya O, Somlo S, Caplan MJ (November 2004).
"Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus" . The Journal of Clinical Investigation . 114 (10): 1433–43.
doi :
10.1172/JCI21753 .
PMC
1052027 .
PMID
15545994 .
^ Low SH, Vasanth S, Larson CH, Mukherjee S, Sharma N, Kinter MT, Kane ME, Obara T, Weimbs T (January 2006).
"Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease" . Developmental Cell . 10 (1): 57–69.
doi :
10.1016/j.devcel.2005.12.005 .
PMID
16399078 .
^ Lal M, Song X, Pluznick JL, Di Giovanni V, Merrick DM, Rosenblum ND, Chauvet V, Gottardi CJ, Pei Y, Caplan MJ (October 2008).
"Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical Wnt signaling" . Human Molecular Genetics . 17 (20): 3105–17.
doi :
10.1093/hmg/ddn208 .
PMC
2722884 .
PMID
18632682 .
^ Shi Y, Mei C, Zhou Q, Wang T, Yu S, Lei J, Ge X, Hu F, Su Q (2018-09-07).
"Structure of the human PKD1-PKD2 complex" . Science . 361 (6406): eaat9819.
doi :
10.1126/science.aat9819 .
ISSN
0036-8075 .
PMID
30093605 .
^ Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J (February 2003). "Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells". Nature Genetics . 33 (2): 129–37.
doi :
10.1038/ng1076 .
PMID
12514735 .
S2CID
23149223 .
^
"Entrez Gene: PKD1 polycystic kidney disease 1 (autosomal dominant)" .
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