Hepatocyte growth factor activator inhibitor-1 has a complex subcellular itinerary.
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Hepatocyte growth factor activator inhibitor-1 has a complex subcellular itinerary. / Godiksen, Sine; Selzer-Plon, Joanna; Pedersen, Esben D K; Abell, Kathrine; Rasmussen, Hanne B; Szabo, Roman; Bugge, Thomas H; Vogel, Lotte K.
In: Biochemical Journal, Vol. 413, No. 2, 2008, p. 251-9.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Hepatocyte growth factor activator inhibitor-1 has a complex subcellular itinerary.
AU - Godiksen, Sine
AU - Selzer-Plon, Joanna
AU - Pedersen, Esben D K
AU - Abell, Kathrine
AU - Rasmussen, Hanne B
AU - Szabo, Roman
AU - Bugge, Thomas H
AU - Vogel, Lotte K.
N1 - Keywords: Animals; Cell Line; Cell Membrane; Dogs; Endocytosis; Exocytosis; Gene Expression Regulation; Lysosomes; Mammary Glands, Animal; Membrane Glycoproteins; Mice; Models, Biological; Protein Transport; Serine Endopeptidases
PY - 2008
Y1 - 2008
N2 - HAI-1 [HGF (hepatocyte growth factor) activator inhibitor-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. In the present study 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 transcytosed 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, plays a role in transporting matriptase as a matriptase-HAI-1 complex from the basolateral plama membrane to the apical plasma membrane, as matriptase is known to interact with prostasin, located at the apical plasma membrane.
AB - HAI-1 [HGF (hepatocyte growth factor) activator inhibitor-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. In the present study 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 transcytosed 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, plays a role in transporting matriptase as a matriptase-HAI-1 complex from the basolateral plama membrane to the apical plasma membrane, as matriptase is known to interact with prostasin, located at the apical plasma membrane.
U2 - 10.1042/BJ20071496
DO - 10.1042/BJ20071496
M3 - Journal article
C2 - 18402552
VL - 413
SP - 251
EP - 259
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 2
ER -
ID: 6093317