ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores.

Mayumi Isokane , Thomas Walter (1) , Robert Mahen , Bianca Nijmeijer , Jean-Karim Hériché (2) , Kota Miura , Stefano Maffini , Miroslav Penchev Ivanov (3) , Tomoya S Kitajima , Jan Peters (4) , Jan Ellenberg (2)

1 CBIO - Centre de Bioinformatique
2 EMBL - European Molecular Biology Laboratory [Heidelberg]
3 MPI-DS
4 IBS - UMR 5075 - Institut de biologie structurale

To prevent genome instability, mitotic exit is delayed until all chromosomes are properly attached to the mitotic spindle by the spindle assembly checkpoint (SAC). In this study, we characterized the function of ARHGEF17, identified in a genome-wide RNA interference screen for human mitosis genes. Through a series of quantitative imaging, biochemical, and biophysical experiments, we showed that ARHGEF17 is essential for SAC activity, because it is the major targeting factor that controls localization of the checkpoint kinase Mps1 to the kinetochore. This mitotic function is mediated by direct interaction of the central domain of ARHGEF17 with Mps1, which is autoregulated by the activity of Mps1 kinase, for which ARHGEF17 is a substrate. This mitosis-specific role is independent of ARHGEF17's RhoGEF activity in interphase. Our study thus assigns a new mitotic function to ARHGEF17 and reveals the molecular mechanism for a key step in SAC establishment.

Domaines: Bio-informatique [q-bio.QM]; Vision par ordinateur et reconnaissance de formes [cs.CV]; Traitement des images [eess.IV]; Bio-Informatique, Biologie Systémique [q-bio.QM]

Mayumi Isokane, Thomas Walter, Robert Mahen, Bianca Nijmeijer, Jean-Karim Hériché, et al.. ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores.. Journal of Cell Biology, 2016, 212 (6), pp.647-59. ⟨10.1083/jcb.201408089⟩. ⟨hal-01427937⟩