Abstract
Tissue factor (TF), a transmembrane glycoprotein, is the cellular receptor of the
coagulation factors VII (FVII) and VIIa (FVIIa). The formation of TF–FVIIa complex
triggers the initiation of the blood coagulation pathway. TF plays an essential role
in haemostasis, but an aberrant expression of TF activity contributes to thrombotic
disorders. In health, TF pro-coagulant activity on cells is controlled tightly to
allow sufficient coagulant activity to achieve haemostasis but not to cause thrombosis.
It is achieved largely by selective localization of TF in the body and encryption
of TF at the cell surface. A vast majority of TF on resting cells exists in an encrypted
state with minimal pro-coagulant activity but becomes pro-thrombotic following cell
injury or activation. At present, the mechanisms that are responsible for TF encryption
and activation (decryption) are not entirely clear, but recent studies provide important
mechanistic insights into these processes. To date, externalization of phosphatidylserine
to the outer leaflet and thiol-disulphide exchange pathways that either turn on and
off the allosteric disulphide bond in TF are shown to play a major role in regulating
TF pro-coagulant activity on cell surfaces. Recent studies showed that sphingomyelin,
a major phospholipid in the outer leaflet of plasma membrane, plays a critical role
in the encryption of TF in resting cells. The present review provides an overview
of recent literature on the above-described mechanisms of TF encryption and decryption
with a particular emphasis on our recent findings.
Keywords
tissue factor - factor VIIa - encryption - decryption - sphingomyelin - phosphatidylserine
- thiol-disulphide exchange pathways
