Investigating a neuronal Kinesin-Myosin Interaction in Dendritic Spines underlying Synaptic Structure and Function

• Applicant: Professor Matthias Kneussel, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 457103565

Kinesin motor proteins mediate long distance transport of molecular cargoes along microtubules that are enriched in neuronal somata, axons and dendrites. Likewise, myosins transport molecules along actin filaments, which are highly abundant underneath the cellular cortex and in dendritic spines. Both cytoskeletal transport systems act largely independent, however microtubules occasionally invade into actin-rich spine protrusions in a synaptic activity-dependent manner.The proposed project is based on the unexpected finding that the kinesin KIF21B physically interacts with myosin Va in neurons. Since Kinesin-Myosin interactions have not been reported in mammals, we aim to investigate the functional relationship of both motors in central neurons.Our preliminary data suggest that myosin Va piggybacks KIF21B into dendritic spines, whereas KIF21B is not important to localize the myosin. Notably, neurons derived from a KIF21B genetic knockout mouse display significantly larger spines and a more stable actin cytoskeleton.Since KIF21B and myosin Va mediate the delivery or recycling of NMDA- and AMPA-type glutamate receptors, I propose to study this novel interaction with respect to synaptic structure and function. I suggest three work packages to investigate the functional relevance of the kinesin-myosin interaction for i.) the invasion of microtubules into spines, ii.) the delivery and recycling of synaptic proteins and iii.) synaptic function and plasticity.Investigating kinesin-myosin interactions at neuronal spine structures can shed new fundamental insights into the functional interplay of microtubule- and actin-dependent transport processes.

• DFG Programme: Research Grants