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Microtubule dynamics and neuronal cargo trafficking during dendrite to axon switching

Final Report Summary - MTSAXONREGENERATION (Microtubule dynamics and neuronal cargo trafficking during dendrite to axon switching)

The brain is formed by more than one hundred billion neurons. These neurons connect each other creating networks in order to receive, process and transmit the information required for brain´s function. Neurons present a complex morphology and they can be divided in two different compartments: the axon and the dendrites. Each compartment presents different morphology, function and composition. The acquisition and maintenance of neuronal polarity is essential for the correct function of neurons, and therefore, for the whole brain. Alterations in neuronal morphology are associated with several human developmental and neurodegenerative diseases. For this reason it is important to understand the cellular mechanisms that underlie the changes during the acquisition of the neuronal polarity. Recent experiments have shown that microtubules are not just passive players involved in axonal outgrowth, but they are actively involved in various phases of neuronal development. Proper microtubule dynamics and organization have been shown to play an important role in the acquisition and maintenance of neuronal polarity. Microtubules can be regulated and organized by some proteins known as microtubule-associated proteins. Several of these proteins have been described; however the role of many of them during neuronal polarization is still unknown. It has been shown that polarized hippocampal neurons retain some plasticity in their polarity. Several studies have shown that neurons can change axonal and dendritic fate, suggesting there is no ‘‘point of no return’’ in neuronal polarization. Here, we combine biochemistry, proteomic analysis, neurobiology and advanced microscopy to characterize the mechanism underlying the rearranged of microtubule dynamics and polarity during the process of dendrite to axon conversion and study the possible role of different microtubule-associated proteins in this process. We have characterized microtubule re-orientation and dynamics during conversion of dendrites into axon in rat hippocampal neurons. In addition, we have performed a screening for different microtubule-associated proteins in order to identify those essential in this process of conversion. Finally, we have correlated events observed during the axon re-specification with the ones occurring at initial polarization stages. The results obtained can be of significant relevance for the elucidation of fundamental aspects of polarity establishment and axonal regeneration. Understanding of these processes may also contribute to develop new treatments based on microtubule manipulation for injured neurons from CNS or different developmental and neurodegenerative diseases where microtubules are altered.

Contact details: Elena Tortosa (e.tortosabinacua@uu.nl)
Division of Cell Biology, Department of Biology, Faculty of Science, Utrecht University
Padualaan 8, 3584 CH, Utrecht, The Netherlands
+31(0)302536840
Cell Biology Department, Faculty of Science, Utrecht University