A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280

Area of Science:

• Molecular biology
• Cell biology
• Biochemistry

Background:

• Tissue factor (TF) is crucial for coagulation, vascular development, and tumor metastasis.
• The molecular mechanisms underlying TF's role in these processes are not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanisms by which TF influences cell adhesion, migration, and intracellular signaling.
• To identify proteins interacting with the cytoplasmic domain of TF.

Main Methods:

• Utilized immobilized TF ligands to study cell adhesion and migration.
• Employed two-hybrid screening to identify TF-interacting proteins.
• Created chimeric molecules to assess the roles of TF's extracellular and cytoplasmic domains.
• Investigated the effect of TF cytoplasmic serine residue mutations on ABP-280 binding and cell spreading.

Main Results:

• Immobilized TF ligands supported cell adhesion, migration, and signaling, independent of RGD peptides.
• Actin-binding protein 280 (ABP-280) was identified as a ligand for the TF cytoplasmic domain.
• ABP-280 recruitment to TF contacts reorganized actin filaments but lacked typical integrin-associated molecules.
• Phosphorylation mimicry (Ser to Asp) enhanced ABP-280 interaction, while alanine mutations abolished it and reduced cell spreading.

Conclusions:

• The TF cytoplasmic domain specifically interacts with ABP-280, providing a molecular basis for TF's role in metastasis and vascular remodeling.
• This interaction is regulated by phosphorylation of TF cytoplasmic serine residues.