Microtubule organization in neurons

Abstract

Neurons serve as the fundamental units for facilitating the transmission of information in the human nervous system. To fulfill this crucial function, neurons possess specialized cell extensions with distinct morphology and function, which is important for the directed flow of information. Specifically, incoming information is received by the dendrites and then transmitted along the axon to the subsequent neuron or effector cell. This morphological and functional distinction between axons and dendrites is referred to as neuron polarity. The microtubule cytoskeleton is a critical factor for neurons to shape their distinctive morphology. Particularly, the distribution of the microtubule cytoskeleton is different between axons and dendrites. In axons, there is a uniform arrangement of microtubules with their plus-ends oriented outward. In contrast, in dendrites, microtubules are organized with a uniform orientation of minus-ends outward in invertebrates, and a mixed orientation in vertebrates. This difference in microtubule organization significantly influences the transportation of cellular cargo to either axons or dendrites. As a result, this regulation ensures the differentiation between these two essential compartments of neuronal architecture. Defects in microtubule polarity can potentially impair neuronal development by disrupting intracellular transport. However, so far, little is known about how the microtubule cytoskeleton acquires their distinct organizational patterns within axons and dendrites. In this thesis, we aimed to elucidate the molecular mechanisms that regulate the organization of the microtubule cytoskeleton in neurons.