Author/Editor		Harris, Peter C
Title		Molecular analysis of autosomal dominant polycystic kidney disease
Translated title		Molekularne analize dominantne autosomske policistične bolezni ledvic
Type		članek
Source		Acta Biol Slov
Vol. and No.		Letnik 43, št. 1-2
Publication year		2000
Volume		str. 117-23
Language		eng
Abstract		Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutation to the PKDl (16p13.3) or PKD2 genes (4q13-23). The ADPKD genes encode proteins, polycystin-1 and polycystin-2, that are different in size and structure, but that have a region of homology and may interact as part of a complex. Polycystin-1 is a large, integral membrane protein (-460kDa) predicted to be involved in cell:cell and/or cell:matrix interactions, while polycystin-2 (-110kDa) is related to voltage activated and TRP channel subunits suggesting a role in ion transport. A wide range of different PKD1 and PKD2 mutations have been detected, most predicted to inactivate the proteins, with a somatic second hit possibly required for focal cyst development. Disruption of the mouse Pkd1 gene Ieads to death in the perinatal period with massive cystic kidneys. Normal nephron induction in Pkd1 mice suggests a role for polycystin-1 later in developing and maintaining the tubular architecture. Recently, two further polycystin-like molecules have been identified, indicating roles for this novel protein family beyond the kidney.
Summary		Dominantna autosomska ledvična policisticna fibroza je posledica mutacije gcnov PKD1 (16p13.3) ali PKD2 (4q13-23). Gena kodirata proteina policistin 1 in policistin 2, ki se strukturno sicer razlikujeta, a imata homologen del in verjetno lahko delujeta kot del večjega kompleksa. policistin-1 je velik integralni membranski protein (-460 kDa). Sodeloval naj bi pri celičnih povezavah ali pri povezavah celic s podlago. Policistin-2 (-110 kDa) je soroden napetostno aktiviranim podenotom TRP kanalčkov, zato je njegova vloga verjetno povezana z ionskim transportom. Na genih PKD1 in PKD2 smo opazili številne mutacije. Večina inaktivira oba proteina, nekatere pa vodijo k nastanku cist. Okvara mišjega PKD1 gena vodi k smrti skotenih osebkov z velikimi policističnimi ledvicami. Indukcija normalnih nefronov pri miših z genom PKD1- kaže na vlogo policistina 1 pri kasnejšem razvoju in vzdrževanju pravilne arhitekture ledvičnih tubulov. Pred kratkim so odkrili dva nova proteina podobna policistinom, kar kaže na njihovo pomembnost tudi v drugih tkivih.
Descriptors		KIDNEY, POLYCYSTIC, AUTOSOMAL DOMINANT MUTATION PEDIGREE