“Polycystin 1”的意思、由来-开放百科全书

Polycystin 1 (often abbreviated to PC1) is a protein that in humans is encoded by the PKD1 gene ^[1]^[2]. 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 ^[3].

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 ^[4]. It has 11 transmembrane domains, a large extracellular N-terminal domain, and a short (about 200 amino acid) cytoplasmic C-terminal domain ^[4]^[5]. 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 ^[4]^[6]. 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 ^[7]. 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 ^[8]^[9].

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.^[10]

PC1 mediates mechanosensation of fluid flow by the primary cilium in the renal epithelium and of mechanical deformation of articular cartilage ^[11].

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.^[12]

References

1. ^{{cite journal | vauthors = Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millán JL, Gamble V, Harris PC | title = The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains | journal = Nature Genetics | volume = 10 | issue = 2 | pages = 151–60 | date = June 1995 | pmid = 7663510 | doi = 10.1038/ng0695-151 }}
2. ^{{cite journal | vauthors = | title = Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium | journal = Cell | volume = 81 | issue = 2 | pages = 289–98 | date = April 1995 | pmid = 7736581 | doi = 10.1016/0092-8674(95)90339-9 }}
3. ^{{cite journal | vauthors = Torres VE, Harris PC, Pirson Y | title = Autosomal dominant polycystic kidney disease | journal = Lancet | volume = 369 | issue = 9569 | pages = 1287–301 | date = April 2007 | pmid = 17434405 | doi = 10.1016/S0140-6736(07)60601-1 }}
4. ^¹²{{cite journal | vauthors = Zhou J | title = Polycystins and primary cilia: primers for cell cycle progression | journal = Annual Review of Physiology | volume = 71 | pages = 83–113 | date = 2009 | pmid = 19572811 | doi = 10.1146/annurev.physiol.70.113006.100621 }}
5. ^{{cite journal | vauthors = Dalagiorgou G, Basdra EK, Papavassiliou AG | title = Polycystin-1: function as a mechanosensor | journal = The International Journal of Biochemistry & Cell Biology | volume = 42 | issue = 10 | pages = 1610–3 | date = October 2010 | pmid = 20601082 | doi = 10.1016/j.biocel.2010.06.017 | url = http://linkinghub.elsevier.com/retrieve/pii/S1357272510002268 }}
6. ^{{cite journal | vauthors = Trudel M, Yao Q, Qian F | title = The Role of G-Protein-Coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kidney Disease | journal = Cells | volume = 5 | issue = 1 | pages = 3 | date = January 2016 | pmid = 26805887 | doi = 10.3390/cells5010003 | url = http://www.mdpi.com/2073-4409/5/1/3 }}
7. ^{{cite journal | vauthors = 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 | title = Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus | journal = The Journal of Clinical Investigation | volume = 114 | issue = 10 | pages = 1433–43 | date = November 2004 | pmid = 15545994 | doi = 10.1172/JCI21753 | pmc = 1052027 }}
8. ^{{cite journal | vauthors = Low SH, Vasanth S, Larson CH, Mukherjee S, Sharma N, Kinter MT, Kane ME, Obara T, Weimbs T | title = Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease | journal = Developmental Cell | volume = 10 | issue = 1 | pages = 57–69 | date = January 2006 | pmid = 16399078 | doi = 10.1016/j.devcel.2005.12.005 }}
9. ^{{cite journal | vauthors = Lal M, Song X, Pluznick JL, Di Giovanni V, Merrick DM, Rosenblum ND, Chauvet V, Gottardi CJ, Pei Y, Caplan MJ | title = Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical Wnt signaling | journal = Human Molecular Genetics | volume = 17 | issue = 20 | pages = 3105–17 | date = October 2008 | pmid = 18632682 | pmc = 2722884 | doi = 10.1093/hmg/ddn208 }}
10. ^{{Cite journal|last=Shi|first=Yigong|last2=Mei|first2=Changlin|last3=Zhou|first3=Qiang|last4=Wang|first4=Tingliang|last5=Yu|first5=Shengqiang|last6=Lei|first6=Jianlin|last7=Ge|first7=Xiaofei|last8=Hu|first8=Feizhuo|last9=Su|first9=Qiang|date=2018-09-07|title=Structure of the human PKD1-PKD2 complex|url=http://science.sciencemag.org/content/361/6406/eaat9819|journal=Science|language=en|volume=361|issue=6406|pages=eaat9819|doi=10.1126/science.aat9819|issn=0036-8075|pmid=30093605}}
11. ^{{cite journal | vauthors = Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J | title = Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells | language = En | journal = Nature Genetics | volume = 33 | issue = 2 | pages = 129–37 | date = February 2003 | pmid = 12514735 | doi = 10.1038/ng1076 | url = http://www.nature.com/articles/ng1076 }}
12. ^{{cite web | title = Entrez Gene: PKD1 polycystic kidney disease 1 (autosomal dominant)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5310| access-date = }}

Protein structure and function

Gene

References

External links