Delineation of proteolytic and non-proteolytic functions of the membrane-anchored serine protease prostasin

Roman Szabo, Taliya Lantsman, Diane E. Peters, Thomas H. Bugge

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The membrane-anchored serine proteases prostasin (PRSS8) and matriptase (ST14) initiate a cell surface proteolytic pathway essential for epithelial function. Mice expressing only catalytically inactive prostasin are viable, unlike prostasin null mice, indicating that at least some prostasin functions are non-proteolytic. Here we used knock-in mice expressing catalytically inactive prostasin (Prss8Ki/Ki) to show that the physiological and pathological functions of prostasin vary in their dependence on its catalytic activity. Whereas prostasin null mice exhibited partial embryonic and complete perinatal lethality, Prss8Ki/Ki mice displayed normal prenatal and postnatal survival. Unexpectedly, catalytically inactive prostasin caused embryonic lethality in mice lacking its cognate inhibitors HAI-1 (SPINT1) or HAI-2 (SPINT2). Proteolytically inactive prostasin, unlike the wild-type protease, was unable to activate matriptase during placentation. Surprisingly, all essential functions of prostasin in embryonic and postnatal development were compensated for by loss of HAI-1, indicating that prostasin is only required for mouse development and overall viability in the presence of this inhibitor. This study expands our knowledge of non-proteolytic functions of membrane-anchored serine proteases and provides unexpected new data on the mechanistic interactions between matriptase and prostasin in the context of epithelial development.

Original languageEnglish (US)
Pages (from-to)2818-2828
Number of pages11
JournalDevelopment (Cambridge)
Issue number15
StatePublished - Aug 1 2016
Externally publishedYes


  • Cell surface proteolysis
  • Epithelial development
  • Placental labyrinth
  • Serine protease

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


Dive into the research topics of 'Delineation of proteolytic and non-proteolytic functions of the membrane-anchored serine protease prostasin'. Together they form a unique fingerprint.

Cite this