The Collagen Receptor Discoidin Domain Receptor 1b Enhances Integrin 1-Mediated Cell Migration by Interacting With Talin and Promoting Rac1 Activation. Academic Article uri icon

abstract

  • Integrins and discoidin domain receptors (DDRs) 1 and 2 promote cell adhesion and migration on both fibrillar and non fibrillar collagens. Collagen I contains DDR and integrin selective binding motifs; however, the relative contribution of these two receptors in regulating cell migration is unclear. DDR1 has five isoforms (DDR1a-e), with most cells expressing the DDR1a and DDR1b isoforms. We show that human embryonic kidney 293 cells expressing DDR1b migrate more than DDR1a expressing cells on DDR selective substrata as well as on collagen I in vitro. In addition, DDR1b expressing cells show increased lung colonization after tail vein injection in nude mice. DDR1a and DDR1b differ from each other by an extra 37 amino acids in the DDR1b cytoplasmic domain. Interestingly, these 37 amino acids contain an NPxY motif which is a central control module within the cytoplasmic domain of integrins and acts by binding scaffold proteins, including talin. Using purified recombinant DDR1 cytoplasmic tail proteins, we show that DDR1b directly binds talin with higher affinity than DDR1a. In cells, DDR1b, but not DDR1a, colocalizes with talin and integrin 1 to focal adhesions and enhances integrin 1-mediated cell migration. Moreover, we show that DDR1b promotes cell migration by enhancing Rac1 activation. Mechanistically DDR1b interacts with the GTPase-activating protein (GAP) Breakpoint cluster region protein (BCR) thus reducing its GAP activity and enhancing Rac activation. Our study identifies DDR1b as a major driver of cell migration and talin and BCR as key players in the interplay between integrins and DDR1b in regulating cell migration.

published proceedings

  • Front Cell Dev Biol

altmetric score

  • 1.5

author list (cited authors)

  • Borza, C. M., Bolas, G., Zhang, X., Browning Monroe, M. B., Zhang, M., Meiler, J., ... Pozzi, A.

citation count

  • 4

complete list of authors

  • Borza, Corina M||Bolas, Gema||Zhang, Xiuqi||Browning Monroe, Mary Beth||Zhang, Ming-Zhi||Meiler, Jens||Skwark, Marcin J||Harris, Raymond C||Lapierre, Lynne A||Goldenring, James R||Hook, Magnus||Rivera, Jose||Brown, Kyle L||Leitinger, Birgit||Tyska, Matthew J||Moser, Markus||Böttcher, Ralph T||Zent, Roy||Pozzi, Ambra

publication date

  • January 2022