Molecular mechanism of the selective recognition of growing microtubule ends by vertebrate +TIPs

• Applicant: Dr. Thomas Surrey
• Subject Area: Biophysics
• Term: from 2008 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 85931720

The microtubule cytoskeleton is crucial for the internal organization of eukaryotic cells. Several microtubule-associated proteins modulate the dynamics of microtubules and provide a link to chromosomes, membrane organelles or the cell cortex. A subclass of these proteins, the so-called microtubule plus-end binding proteins (+TIPs), have the remarkable property of selectively binding to the growing plus ends of microtubules. These proteins have several essential functions. They are crucial for proper cell division, involved in signalling or responsible for the establishment of cell polarity. Defective forms of these proteins can lead to cancer. The molecular mechanism, however, by which these proteins recognize the dynamic microtubule end and how they affect microtubule dynamics is not understood. This is a result of the complexity of the microtubule plus-end tracking system that consists of several interacting proteins in vivo. Another problem has been that plus-end tracking could not be reconstituted in vitro. Here we will reconstitute with several vertebrate +TIPs dynamic plus-end tracking in vitro. Using biochemical techniques and time-lapse fluorescence microscopy down to the single molecule level, we will analyze quantitatively in a minimal and well-controlled system the molecular interactions and the dynamics underlying the phenomenon of microtubule plus-end tracking. We aim at elucidating how combinatorial effects between mutually interacting +TIPs define the functioning of the multi-component plus-end tracking system at a molecular level. This work will lead to a molecular understanding of the functioning of a dynamic protein interaction network showing complex dynamic behavior.

• DFG Programme: Research Grants