Mitotic functions of MTUS1-defined Microtubule bundles

• Applicant: Professor Dr. Oliver Gruß
• Subject Area: Cell Biology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 329979611

Microtubule associated proteins (MAPs) govern the function of microtubules (MT) in interphase and in mitosis. In previous approaches, we had identified a novel MT-associated protein complex that regulates the reorganisation of MT upon entry into mitosis in blastomeres during early development and in somatic cells. Recently, we discovered a novel component of this complex, Microtubule-associated tumor suppressor 1, MTUS1. Our preliminary data show that MTUS1 displays a unique MT binding and bundling pattern crosslinking two MT polymers in a stereotypic manner side by side. Modulating this bundling activity is ideally suited to regulate MT at the entry and during mitosis. We suggest a project to analyse the molecular mode of action of MTUS1 in mitosis. Our model of MTUS1 action includes several key points that can be experimentally tested, first and foremost a regulated protein conformation switch that enables or, vice versa, abolishes MTUS1 dimerization as the basis of its MT bundling activity. Dimerization of an “open” conformation generates a divalent MT binding unit consistent with MT tandem formation. We will test if the switch to dimeric MTUS1 and back, and thus MT tandem formation, may be guided by Rho family members and an abundant phosphorylation site in the C-terminus. We propose a project to analyse MTUS1 function, alone and in cooperation with its homologue MTUS2, as a paradigm of the action of MAPs in cell division. We aim at understanding how MTUS1 activity in bundling of MT tandems functions before, during and after mitosis in different experimental set-ups. Specific mutant variants (dimerization defective, Rho binding defective, MT binding defective, phosphorylation deficient) will be analysed consistently in vitro (i.e. using purified proteins), “ex vivo” (i.e. in Xenopus cell free extracts) and in vivo (i.e. in intact cells).

• DFG Programme: Research Grants