Direct Interaction between TalinB and Rap1 is necessary for adhesion of Dictyostelium cells

The small G-protein Rap1 is an important regulator of cellular adhesion in Dictyostelium, however so far the downstream signalling pathways for cell adhesion are not completely characterized. In mammalian cells talin is crucial for adhesion and Rap1 was shown to be a key regulator of talin signalling.

Dictyostelium Rap1 directly binds to TalinB via the conserved RA domain. This interaction is critical for adhesion, which becomes essential for high adhesive force demanding processes, like morphogenesis during multicellular development of Dictyostelium. In mammalian cells the established Rap1-talin interaction is indirect and acts through the scaffold protein - RIAM. Interestingly, direct binding of mouse Rap1 to the RA domain of Talin1 has recently been demonstrated.

In a proteomic screen we identified TalinB as a potential Rap1 effector in Dictyostelium. In subsequent pull-down experiments we demonstrate that the Ras association (RA) domain of TalinB interacts specifically with active Rap1. Studies with a mutated RA domain revealed that the RA domain is essential for TalinB-Rap1 interaction, and that this interaction contributes to cell-substrate adhesion during single-celled growth and is crucial for cell-cell adhesion during multicellular development. Conclusions: Dictyostelium Rap1 directly binds to TalinB via the conserved RA domain. This interaction is critical for adhesion, which becomes essential for high adhesive force demanding processes, like morphogenesis during multicellular development of Dictyostelium. In mammalian cells the established Rap1-talin interaction is indirect and acts through the scaffold protein - RIAM. Interestingly, direct binding of mouse Rap1 to the RA domain of Talin1 has recently been demonstrated.