Ein SH3-Domänen basiertes Proteininteraktionsnetzwerk reguliert den Eintritt in die Zelltrennug am Ende der Zytokinese
Zusammenfassung der Projektergebnisse
Boi1 and Boi1 are the effectors of the No-cut pathway, whereas Fir1 is the central component of the Eco pathway. Both pathways regulate different steps of cytokinesis. Boi1 and Boi2 are supposed to stop abscission when the genomic material is not fully separated between mother and daughter cell, whereas Fir1 is supposed to stop cell separation as long abscission is not completed. Furthermore, active Cdc42 inhibits abscission by downregulating the activity of Rho1 and probably the activities of other, not yet discovered pathways. We could reconstruct a protein interaction network that links the major components of all three pathways into one network below the cell separation site. The central hinges of this network are provided by the SH3 domains of Boi1, Boi2, Bem1, Cyk3, Bud14, and Hof1 that all interact with small proline-rich motives situated within non-structured regions of their target proteins. We discovered that this network anchors during cytokinesis the Bem1-Cdc24 module to the bud neck. Here the SH3 domain of Bem1 interacts with a central motive in Boi1 and Boi2 that use their own SH3 domains to bind to the bud neck components Nba1 and Fir1. In this interaction state, the SH3-domain of Bem1 is blocked and will not interact with Ste20 to down regulate the abscission pathway. As we detect interactions between Bem1 and Ste20 also during the late phases of cytokinesis, we postulate a fine-tuned balance between the Boi1/2-Bem1 and the Ste20-Bem1 interaction states that controls the progression through abscission. Progress of cell separation clearly depends on the fusion of secretory vesicles with the constricting plasma membrane. The newly discovered physical link between the exocyst and Nba1 provides a basis for understanding how the regulation of exocytosis might be incorporated into the herein characterized networks.
Projektbezogene Publikationen (Auswahl)
- 2020. A time-resolved interaction analysis of Bem1 reconstructs the flow of Cdc42 during polar growth. Life.Sci.Alliance. 3:10
Grinhagens, S., A. Dünkler, Y. Wu, L. Rieger, P. Brenner, T. Gronemeyer, M.A. Mulaw, and N. Johnsson
(Siehe online unter https://doi.org/10.26508/lsa.202000813)
