Mechanism of dynein targeting, anchorage and activation at microtubule plus-ends

• Applicant: Professor Dr. Gero Steinberg
• Subject Area: Cell Biology
• Term: from 2003 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5401119

Recently, we identified cytoplasmic dynein from Ustilago maydis. Surprisingly, Ustilago dynein shares several features with dyneins from higher eukaryotes that other fungal dyneins not have. This includes a large C-terminal region of 31 kD and a lethal null mutant phenotype. Furthermore, dyneins from higher eukaryotes and U. maydis localize to the spindle, which may be due to the fact that U. maydis undergoes an "open mitosis", whereas the nuclear envelope remains intact in all other fungal model systems. These similarities between mitosis in vertebrates and U. maydis suggest that the conserved 31 kD domain of dynein exerts an essential function in the "open mitosis". Preliminary evidence demonstrates that the lethality of mutations in dynein genes can be rescued by destabilizing microtubules (MTs) with benomyl, indicating that the essential function of dynein is due to an influence on MT dynamics. In the project proposed here we wish to analyze the role of the C-terminal dynein domain and its connection to the putatively essential function of dynein in the "open mitosis" of U. maydis. In addition, the importance of MT dynamics in dynein function will be our focus. The following questions will guide us: (1) What is the mitotic function of dynein in the spindle of U. maydis, (2) is their a connection between this role in mitosis and the ~31 kD region that have higher eukaryotes and U. maydis in common, and (3) which essential role of U. maydis dynein depends on its influence on microtubule dynamics. In understanding dyneins role in "open" mitosis of U. maydis we hope to elucidate mitotic mechanisms in higher eukaryotes, in general.

• DFG Programme: Research Grants