Renin, a secretory glycoprotein, acquires phosphomannosyl residues

P. L. Faust, J. M. Chirgwin, S. Kornfeld

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Renin is an aspartyl protease which is highly homologous to the lysosomal aspartyl protease cathepsin D. During its biosynthesis, cathepsin D acquires phosphomannosyl residues that enable it to bind to the mannose 6-phosphate (Man-6-P) receptor and to be targeted to lysosomes. The phosphorylation of lysosomal enzymes by UDP-GlcNAc/lysosomal enzyme N-acetylglucosaminylphosphotransferase (phosphotransferase) occurs by recognition of a protein domain that is thought to be present only on lysosomal enzymes. In order to determine whether renin, being structurally similar to cathepsin D, also acquires phospomannosyl residues, human renin was expressed from cloned DNA in Xenopus oocytes, and a mouse L cell line and its biosynthesis and posttranslational modifications were characterized. In Xenopus occytes, the majority of the renin remained intracellular and underwent a proteolytic cleavage which removed the propiece. Most of the renin synthesized by oocytes was able to bind to a Man-6-P receptor affinity column (53%, 57%, and 90%, in different experiments), indicating the presence of phosphomannosyl residues. In the L cells, the majority of the renin was secreted but 5-6% of the renin molecules contained phosphomannosyl residues as demonstrated by binding of [35S]methionine-labeled renin to the Man-6-P receptor as well as direct analysis of [2-3H]mannose-labeled oligosaccharides. Although the level of renin phosphorylation differed greatly between the two cell types examined, these results demonstrate that renin is recognized by the phosphotransferase and suggest that renin contains at least part of the lysosomal protein recognition domain.

Original languageEnglish (US)
Pages (from-to)1947-1955
Number of pages9
JournalJournal of Cell Biology
Volume105
Issue number5
DOIs
StatePublished - 1987

ASJC Scopus subject areas

  • Cell Biology

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