Abstract
A polarized arrangement of neuronal microtubule arrays is the foundation of membrane trafficking and subcellular compartmentalization. Conserved among both invertebrates and vertebrates, axons contain exclusively 'plus-end-out' microtubules while dendrites contain a high percentage of 'minus-end-out' microtubules, the origins of which have been a mystery. Here we show that in Caenorhabditis elegans the dendritic growth cone contains a non-centrosomal microtubule organizing center (MTOC), which generates minus-end-out microtubules along outgrowing dendrites and plus-end-out microtubules in the growth cone. RAB-11-positive endosomes accumulate in this region and co-migrate with the microtubule nucleation complex γ-TuRC. The MTOC tracks the extending growth cone by kinesin-1/UNC-116-mediated endosome movements on distal plus-end-out microtubules and dynein clusters this advancing MTOC. Critically, perturbation of the function or localization of the MTOC causes reversed microtubule polarity in dendrites. These findings unveil the endosome-localized dendritic MTOC as a critical organelle for establishing axon-dendrite polarity.
Highlights
The ability of our nervous system to function rests on polarized transport within the axons and dendrites of neurons, a task performed by molecular motors running on a polarized microtubule (MT) network
An active microtubule organizing center (MTOC) localizes to the growth cone of the outgrowing primary dendrite We explored the origins of MT organization using the PVD neuron in C. elegans, a sensory neuron with stereotypical morphology of its axon and non-ciliated dendrites (Albeg et al, 2011)
To investigate the establishment of minus-end-out MTs during dendrite outgrowth, we visualized the endogenous localization of the MT plus-end tracking protein EBP-2::GFP/EB1 in developing PVD anterior dendrites and found that numerous EBP-2 comets emerged from a single region within the distal neurite, suggesting the presence of a dendritic growth cone MTOC
Summary
The ability of our nervous system to function rests on polarized transport within the axons and dendrites of neurons, a task performed by molecular motors running on a polarized microtubule (MT) network. In mature neurons, MTs are organized along the length of neurites with specific orientation; axons contain exclusively plus-end-out MTs, while dendrites have predominantly minus-end-out or both plus-end-out and minus-end-out MTs in invertebrate and vertebrate species, respectively (Baas et al, 1988; Stepanova et al, 2003; Stone et al, 2008). This specific MT organization is critical for normal intracellular vesicular trafficking as different cargoes engage either plus-end-directed or minus-enddirected motor proteins. Despite the importance of proper MT organization to neuronal function, how MTs initially adopt these patterns during neuronal development is largely unknown
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