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Article Dans Une Revue Biochemical Journal Année : 2008

Hepatocyte growth factor activator inhibitor-1 has a complex subcellular itinerary

Sine Godiksen
  • Fonction : Auteur
Joanna Selzer-Plon
  • Fonction : Auteur
Esben D.K. Pedersen
  • Fonction : Auteur
Kathrine Abell
  • Fonction : Auteur
Hanne Borger Rasmussen
  • Fonction : Auteur
Roman Szabo
  • Fonction : Auteur
Thomas H Bugge
  • Fonction : Auteur

Résumé

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a Kunitz-type transmembrane serine protease inhibitor that forms inhibitor complexes with the trypsin-like serine protease, matriptase. HAI-1 is essential for mouse placental development and embryo survival and together with matriptase it is a key regulator of carcinogenesis. HAI-1 is expressed in polarized epithelial cells, which have the plasma membrane divided by tight junctions into an apical and a basolateral domain. Here we show that HAI-1 at steady state is mainly located on the basolateral membrane of both Madin-Darby Canine Kidney cells and mammary gland epithelial cells. After biosynthesis HAI-1 is exocytosed mainly to the basolateral plasma membrane from where 15% of the HAI-1 molecules are proteolytically cleaved and released into the basolateral medium. The remaining membrane-associated HAI-1 is endocytosed and then recycles between the basolateral plasma membrane and endosomes for hours until it is trancytosed to the apical plasma membrane. Minor amounts of HAI-1 present at the apical plasma membrane are proteolytically cleaved and released into the apical medium. Full-length membrane-bound HAI-1 has a half life of 1.5 h and is eventually degraded in the lysosomes, whereas proteolytically released HAI-1 is more stable. HAI-1 is co-localized with its cognate protease, matriptase, at the basolateral plasma membrane. We suggest that HAI-1, in addition to its protease inhibitory function, play a role in transportingmatriptase from the basolateral plama membrane to the apical plasma membrane, as matriptase is known to interact with prostasin, located at the apical plasma membrane.

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Dates et versions

hal-00478909 , version 1 (30-04-2010)

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Sine Godiksen, Joanna Selzer-Plon, Esben D.K. Pedersen, Kathrine Abell, Hanne Borger Rasmussen, et al.. Hepatocyte growth factor activator inhibitor-1 has a complex subcellular itinerary. Biochemical Journal, 2008, 413 (2), pp.251-259. ⟨10.1042/BJ20071496⟩. ⟨hal-00478909⟩

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