Integrin-based adhesion compartmentalizes ALK3 of the BMPRII to control cell adhesion and migration

Decoupling of the functions between ALK3 and BMPRII: ALK3 segregation in focal adhesion is BMP2 dependent and BMPRII independent to control cell adhesion processes and SMAD stability. The spatial organization of cell-surface receptors is fundamental for the coordination of biological responses to physical and biochemical cues of the extracellular matrix. How serine/threonine kinase receptors, ALK3-BMPRII, cooperate with integrins upon BMP2 to drive cell migration is unknown. Whether the dynamics between integrins and BMP receptors intertwine in space and time to guide adhesive processes is yet to be elucidated. We found that BMP2 stimulation controls the spatial organization of BMPRs by segregating ALK3 from BMPRII into beta 3 integrin-containing focal adhesions. The selective recruitment of ALK3 to focal adhesions requires beta 3 integrin engagement and ALK3 activation. BMP2 controls the partitioning of immobilized ALK3 within and outside focal adhesions according to single-protein tracking and super-resolution imaging. The spatial control of ALK3 in focal adhesions by optogenetics indicates that ALK3 acts as an adhesive receptor by eliciting cell spreading required for cell migration. ALK3 segregation from BMPRII in integrin-based adhesions is a key aspect of the spatio-temporal control of BMPR signaling.

Automated summary

This article investigates the decoupling of functions between ALK3 and BMPRII, and demonstrates that BMP2 stimulation controls the spatial organization of BMPRs by segregating ALK3 from BMPRII and recruiting it to beta 3 integrin-containing focal adhesions. The findings suggest that the spatial control of ALK3 in focal adhesions is crucial for cell adhesion processes and the stability of SMAD. The study sheds light on the interplay between integrins and BMP receptors in guiding adhesive processes.