KINSELECT · Microtubule organisation and polarized transport of kinesins in neurons

Microtubule organisation and polarized transport of kinesins in neurons

The human brain consists of approximately 100 billion neurons that are interconnected to form functional neuronal circuits. The ability of neurons to receive, process and transmit information relies on their polarized organisation into axons and dendrites. This high degree of polarization and the underlying functional compartmentalization present major challenges for sorting and distribution of sub-cellular components. Impairment of intracellular transport has been linked to certain neurodegenerative diseases such as Alzheimer’s disease and Amyotrophic Lateral Sclerosis. Therefore, understanding the molecular mechanisms that govern polarized transport is a central challenge in the field of neurobiology. Microtubules (MTs) are polarized cytoskeletal polymers important for the proliferation, morphology, and intracellular organisation of cells because they support cell division, polarization and intracellular transport. MTs serve as tracks for both kinesin and dynein motor proteins, which move in opposite directions towards the plus- and minus-end of the MT, respectively. Therefore, in neurons, the MT cytoskeleton enables distinct motor proteins to transport cargoes selectively into either axons or dendrites. Whereas axonal MTs are uniformly oriented, dendritic MTs in mammalian neurons have mixed orientations; and remarkably, most MTs in mature neurons are not connected to the centrosome, the main MT organizing centre (MTOC) in other cell types. However, the molecular mechanisms regulating non-centrosomal MTs nucleation and positioning and therefore proper MT polarity in different neuronal compartments have remained unclear. Furthermore, several plus-end directed motor proteins are selective for the axon, while others target both the axon and dendrites. It is widely assumed that these fundamental differences in selectivity are encoded by the MT network; however, the molecular organisation design that ensure axon-selective transport have remained unresolved. By combining molecular engineering, live cell imaging and super-resolution microscopy, we aimed at determining the connection between microtubule organisation and polarized transport in neurons.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз