Thrombospondin-1 Is a Contact Sensor Triggering Adhesion in T Cells and Platelets While Differentially Regulating 2D...

Area of Science:

• Cell Biology
• Biochemistry
• Immunology

Background:

• Cell adhesion and motility are crucial biological processes, yet their regulatory mechanisms remain incompletely understood.
• Thrombospondin-1 (TSP-1) is a matricellular protein implicated in various cellular functions, including cell-matrix interactions.

Purpose of the Study:

• To elucidate the mechanism by which cells sense their microenvironment to regulate adhesion and motility.
• To investigate the role of TSP-1 in T cell and platelet adhesion and migration.

Main Methods:

• Investigated TSP-1 cleavage by urokinase plasminogen activator (uPA) using zymography and inhibitor studies.
• Examined TSP-1-mediated cell shape changes and migration in T cells and platelets on 2D and 3D substrates.
• Assessed the involvement of LRP1 and CXCL12 in TSP-1 signaling pathways.

Main Results:

• TSP-1's C-terminus senses cell contact, initiating N-terminal cleavage by uPA, leading to adhesion and cytoplasmic spreading.
• In 2D, TSP-1 promotes polar cell shape independently of LRP1, while LRP1 interaction induces migration via TSP-1 internalization.
• 3D migration and polar cell shape development are mediated by direct TSP-1/LRP1 interaction; TSP-1 cleavage inhibits 3D migration, whereas CXCL12 stimulates it.

Conclusions:

• TSP-1 functions as a contact-sensing molecule that triggers adhesion in platelets and T cells.
• TSP-1 regulates T cell motility by driving and modulating cell polarity and migration in both 2D and 3D contexts.
• TSP-1 cleavage by uPA is a critical regulatory step influencing cell adhesion and motility outcomes.