Chemical Genetics with SP600125 Reveals That Mps1 Protein Kinase Works as a Regulatory Element in Post-embryonic...

The "spindle assembly checkpoint" (SAC) is a regulatory pathway that monitors the correct anchoring of the mitotic spindle microtubules to chromosomes during the metaphase-anaphase transition. The protein kinase monopolar spindle 1 (Mps1) is a key SAC component and is considered a promising target for antitumor drugs. This has led to the development of different inhibitory molecules that have helped to elucidate the Mps1 functions in the cell cycle. However, in plants, the catalytic mechanisms and roles of Mps1 during cell proliferation remain unknown. Here, we show that Arabidopsis thaliana's Mps1 (AtMps1) has a similar catalytic structure to that observed in humans (Homo sapiens' Mps1HsMps1) and that its inhibition by SP600125 hinders postgerminative development. Further, our computational docking studies strongly suggest that both HsMps1 and AtMps1 interact with SP600125 in a similar manner and that plant proteins have topologically conserved protein-protein interaction motifs in their kinase domains. Furthermore, using A. thaliana as an experimental model demonstrates that Mps1 activity is essential for cell proliferation and postgerminative development and that SP600125 effects are reversible. Our experiments open new possibilities for understanding the mechanisms of the Mps1 protein using plants as experimental models. They also show that chemical genetics is a robust alternative for studies of plant development.