Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure.

Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Research Abstract Details 

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Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Abstract Text:

Shengqiang Yu,Karl Hackmann,Jianggang Gao,Xiaobing He,Klaus Piontek,Miguel A ,Luis F Menezes,Hangxue Xu,Gregory G Germino,Jian Zuo,Feng Qian,Shengqiang Yu,Karl Hackmann,Jianggang Gao,Xiaobing He,Klaus Piontek,Miguel A ,Luis F Menezes,Hangxue Xu,Gregory G Germino,Jian Zuo,Feng Qian,

Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its function causes cystogenesis in human autosomal dominant polycystic kidney disease. We have previously shown that recombinant human PC1 is cis-autoproteolytically cleaved at the G protein-coupled receptor proteolytic site domain. To investigate the role of cleavage in vivo, we generated by gene targeting a Pkd1 knockin mouse (Pkd1(V/V)) that expresses noncleavable PC1. The Pkd1(V/V) mice show a hypomorphic phenotype, characterized by a delayed onset and distal nephron segment involvement of cystogenesis at postnatal maturation stage. We show that PC1 is ubiquitously and incompletely cleaved in wild-type mice, so that uncleaved and cleaved PC1 molecules coexist. Our study establishes a critical but restricted role of cleavage for PC1 function and suggests a differential function of the two types of PC1 molecules in vivo.

Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Publishing Authors By Initials

S Yu,K Hackmann,J Gao,X He,K Piontek,MA ,LF Menezes,H Xu,GG Germino,J Zuo,F Qian,S Yu,K Hackmann,J Gao,X He,K Piontek,MA ,LF Menezes,H Xu,GG Germino,J Zuo,F Qian,

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Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 18688-93

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 1091-6490

DAY: 14

MONTH: 11

YEAR: 2007

Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure.

AFFILIATION: Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK51259

ACRONYM: DK

MEDLINETA: Proc Natl Acad Sci U S A

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