Microtubule dynamics in postsynaptic structure and function: role of the microtubule severing enzyme katanin

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The microtubule cytoskeleton regulates different cellular processes including cell division, cell adhesion and cell migration. Furthermore, it participates in the structure and function of cells and acts as a track for the transport of molecular motors and their cargoes. Severing enzymes, such as spastin, katanin and fidgetin sever microtubules and participate in the regulation of microtubule dynamics. With respect to the delivery and function of neuronal synapses, it is currently unknown whether and how microtubule severing plays a role in this context.This research proposal aims to use a newly established conditional katanin knockout mouse (for postnatal, neuron-specific katanin depletion) and dominant-negative approaches, to unravel the role of katanin-mediated microtubule severing in the delivery, structure and function of neuronal synapses. A major goal is to study the dynamics of microtubules, their subcellular localization and their transient entry into dendritic spines in the absence of katanin gene expression or function, respectively. Moreover, the project asks whether such dynamic processes affect the binding of microtubule associated proteins (MAPs) and molecular motors to microtubules. Using time-lapse video microscopy in living neurons, it is a goal to compare the transport of synaptic proteins across genotypes. Imaging data should be complemented by molecular and biochemical assays. Finally, electrophysiological analysis should clarify whether katanin depletion affects synaptic transmission. If katanin depletion alters the structure and/or function of synapses, further assays to study neuronal network plasticity and mouse behaviour should be applied to understand a potential contribution of microtubule severing for network function and cognition.