PIEZO1 and PECAM1 interact at cell-cell junctions and partner in endothelial force sensing

Area of Science:

• Endothelial mechanotransduction
• Cell adhesion biology
• Molecular cell biology

Background:

• Endothelial cells sense shear stress via PIEZO1 channels and PECAM1-based complexes.
• The relationship between PIEZO1 and PECAM1 in shear stress sensing is not well understood.

Purpose of the Study:

• To investigate the interaction between PIEZO1 and PECAM1 in endothelial cells.
• To determine the role of this interaction in shear stress sensing and junctional remodeling.

Main Methods:

• In situ tagging of endogenous PIEZO1 in mice.
• High-resolution microscopy and reconstitution studies.
• Analysis of protein interactions under varying shear stress conditions.

Main Results:

• PIEZO1 and PECAM1 show in situ overlap and direct interaction, with PECAM1 directing PIEZO1 to cell-cell junctions.
• PECAM1's extracellular N-terminus and shear stress-sensitive C-terminus are crucial for PIEZO1 localization.
• CDH5 also drives PIEZO1 to junctions, with a dynamic interaction that increases with shear stress.
• PIEZO1 is essential for Ca2+-dependent adherens junction formation and cytoskeletal organization.

Conclusions:

• PIEZO1 localizes to cell junctions through interaction with adhesion molecules like PECAM1 and CDH5.
• This localization facilitates force-dependent calcium entry for junctional remodeling in response to shear stress.
• PIEZO1 and adhesion molecules cooperate to adapt endothelial junctional structure to mechanical demands.