Berlin 2018 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 6: Cytoskeletal Filaments I

BP 6.7: Vortrag

Montag, 12. März 2018, 16:45–17:00, H 1058

Dynactin stabilises microtubules to establish their uniform orientation in neuronal axons — •Maximilian Jakobs and Kristian Franze — Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

The microtubule (MT) cytoskeleton in neuronal axons is highly oriented with almost all MTs pointing with their growing end (+end) away from the cell body (+end out). Motor proteins rely on this orientation to move cellular cargo to the distal regions of the axon. Despite 30 years of research, the mechanism that establishes MT orientation remains unknown. We here analysed MT growth with supervised machine learning in D. melanogaster neurons, complemented by an analytical model of MT growth. We found that +end out MTs grow for longer times than oppositely oriented MTs (−end out). According to our model, this leads to dramatic differences in average MT lengths, so that −end out MTs are short and unstable. Additionally, we found evidence that dynactin is responsible for the differences in growth times by promoting growth at the axonal tip through a molecular gradient. These findings suggest a simple mechanism that organises axonal MTs. First, +end out MTs are stabilized by distally located dynactin. Subsequently, the short −end out MTs depolymerize or reorient, leaving only +end out MTs in the axon. Our results pave the way towards a deeper understanding of how the cytoskeleton in neurons orients to support molecular transport, potentially shedding light on pathologies that are characterized by axonal transport deficiencies such as Alzheimers disease.