Single kinesin-8 microtubule depolymerization activity investigated with optical tweezers

• Applicant: Dr. Anita Jannasch
• Subject Area: Biophysics
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 286126442

Microtubules are highly dynamic cellular filaments. The end of microtubules alternate between periods of slow growth and rapid shortening known as dynamic instability. An accurate control of this instability is crucial for many intracellular processes like cell division. In vivo and in vitro studies showed that one of the factors responsible for destabilizing microtubules are motor proteins of the kinesin-8 family. Kinesin-8 can cross-link microtubules and depolymerize them in a length-dependent manner by interacting with their ends. Despite several studies addressing the function of the kinesin-8 motor protein, the molecular mechanism of how kinesin-8 depolymerizes microtubules is still unclear. One hypothesis is that kinesin-8 act cooperatively to depolymerize microtubules. The aim of this proposal is to measure depolymerization forces and test the cooperative depolymerization model by resolving the end-binding activity of single kinesin-8 motors using high-resolution optical tweezers as a sensitive position and force transducer. Understanding the mechanics of kinesin-8 end activity will provide important insights for cell division with implications for future cancer research.

• DFG Programme: Research Grants