Abstract
Neurons display a highly polarized microtubule network that mediates trafficking throughout the extensive cytoplasm and is crucial for neuronal differentiation and function. In newborn migrating neurons, the microtubule network is organized by the centrosome. During neuron maturation, however, the centrosome gradually loses this activity, and how microtubules are organized in more mature neurons remains poorly understood. Here, we demonstrate that microtubule organization in post-mitotic neurons strongly depends on non-centrosomal nucleation mediated by augmin and by the nucleator γTuRC. Disruption of either complex not only reduces microtubule density but also microtubule bundling. These microtubule defects impair neurite formation, interfere with axon specification and growth, and disrupt axonal trafficking. In axons augmin does not merely mediate nucleation of microtubules but ensures their uniform plus end-out orientation. Thus, the augmin-γTuRC module, initially identified in mitotic cells, may be commonly used to generate and maintain microtubule configurations with specific polarity.
Highlights
Neurons display a highly polarized microtubule network that mediates trafficking throughout the extensive cytoplasm and is crucial for neuronal differentiation and function
Our results reveal the versatility of the augmin-g-tubulin ring complexes (gTuRCs) module and suggest that mature neurons may not require any specific microtubule organizing centre (MTOC) to maintain the organization of their extensive microtubule network
To address whether gTuRC may have a role in post-mitotic neurons we first determined the levels of gTuRC subunits at the centrosome of murine cultured hippocampal neurons and in the soluble fraction of hippocampal lysates
Summary
Neurons display a highly polarized microtubule network that mediates trafficking throughout the extensive cytoplasm and is crucial for neuronal differentiation and function. Experimental removal of the centrosome affected neither axon growth in rodent cultured hippocampal neurons[13] nor neuronal microtubule organization and morphogenesis in flies[1,2,3,14,15] These results led to the conclusion that microtubules in post-mitotic neurons can be nucleated by a non-centrosomal mechanism. In addition to nucleation at MTOCs, microtubules can be nucleated from the lateral surface of pre-existing or ‘mother’ microtubules Such a mechanism generates microtubules within mitotic and meiotic spindles and within the interphase cortical microtubule array in plants, independently of centrosomes[24]. This nucleation mode requires another multi-subunit protein complex termed augmin, which recruits gTuRC to microtubule lattices to nucleate microtubule branches[25,26,27,28,29]
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