Motors on track: Insights in kinesin function and regulation

Abstract

A network of microtubule filaments serves as a highway system in our cells. Motor proteins, like kinesin move along microtubules to transport cargo such as cell organelles. There are over 40 different types of kinesins which all have a unique function in the different cell types of our body. In this thesis, we looked at the function and regulation of some of these motor proteins.

Kinesin-1 is one of the best-studied kinesin motors. In the first part of the thesis we show that members of the MAP7 family of microtubule-associated proteins are essential for the motility of kinesin-1 in cells. MAP7 proteins help this kinesin to land on a microtubule and in addition stimulate kinesin-1 activity through a direct interaction.

In the second part of the thesis, we looked at two less well-studied kinesin motors: MKLP2 and KIF21B. The MKLP2 kinesin is involved in the process of cell division, but its molecular activity was not well understood. Through a molecular characterization of MKLP2, we now know that the motor can slowly move along microtubules and transport the Chromosomal Passenger Complex, an import signaling complex for dividing cells. KIF21B is specifically expressed in T cells, an essential type of cells of our immune system. In these cells, KIF21B regulates microtubule length by stimulating breakdown of the polymer at the growing end. This activity is important for a rapid reorganization of the microtubule network, a process that is induced when T cells communicate with other cells or have to eliminate sick cells.