Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations

Feng Qian, Alessandra Boletta, Anil K. Bhunia, Hangxue Xu, Lijuan Liu, Ali K. Ahrabi, Terry J. Watnick, Fang Zhou, Gregory G. Germino

Research output: Contribution to journalArticle

Abstract

Polycystin-1 plays an essential role in renal tubular morphogenesis, and disruption of its function causes cystogenesis in human autosomal-dominant polycystic kidney disease (ADPKD). We demonstrated that polycystin-1 undergoes cleavage at G protein coupled receptor proteolytic site in a process that requires the receptor for egg jelly domain. Most of the N-terminal fragment remains tethered at the cell surface, although a small amount is secreted. PKD1-associated mutations in the receptor for egg jelly domain disrupt cleavage, abolish the ability of polycystin-1 to activate signal transducer and activator of transcription-1, and induce tubulogenesis in vitro. We conclude that the cleavage of polycystin-1 is likely essential for its biologic activity.

Original languageEnglish
Pages (from-to)16981-16986
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number26
DOIs
Publication statusPublished - Dec 24 2002

ASJC Scopus subject areas

  • Genetics
  • General

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