Cellular localization and trafficking of tissue factor.
Tissue factor (TF) is the cellular receptor for clotting factor VIIa (FVIIa). The formation of TF-FVIIa complexes on cell surfaces triggers the activation of coagulation cascade and cell signaling. In the present study, we characterized the subcellular distribution of TF and its transport in fibroblasts by dual immunofluorescence confocal microscopy and biochemical methods. Our data show that a majority of TF resides in various intracellular compartments, predominantly in the Golgi. Tissue factor at the cell surface is localized in cholesterol-rich lipid rafts and extensively colocalized with caveolin-1. FVIIa binding to TF induces the internalization of TF. Of interest, we found that TF-FVIIa complex formation at the cell surface leads to TF mobilization from the Golgi with a resultant increase in TF expression at the cell surface. This process is dependent on FVIIa protease activity. Overall, the present data suggest a novel mechanism for TF expression at the cell surface by FVIIa. This mechanism could play an important role in hemostasis in response to vascular injury by increasing TF activity where and when it is needed.
Mandal
Samir K
SK
Biomedical Research Division, The University of Texas Health Center at Tyler, TX 75708, USA.
Pendurthi
Usha R
UR
Rao
L Vijaya Mohan
LV
D001777:Blood Coagulation / Q000502:physiology; D001808:Blood Vessels / Q000293:injuries / Q000378:metabolism; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology; D015942:Factor VIIa / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006487:Hemostasis; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D018613:Microscopy, Confocal; D046912:Multiprotein Complexes / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D013925:Thromboplastin / Q000378:metabolism*
D046912:Multiprotein Complexes; D013925:Thromboplastin; D015942:Factor VIIa