Abstract
Neurons contain polarised microtubule arrays essential for neuronal function. How microtubule nucleation and polarity are regulated within neurons remains unclear. We show that γ-tubulin localises asymmetrically to the somatic Golgi within Drosophila neurons. Microtubules originate from the Golgi with an initial growth preference towards the axon. Their growing plus ends also turn towards and into the axon, adding to the plus-end-out microtubule pool. Any plus ends that reach a dendrite, however, do not readily enter, maintaining minus-end-out polarity. Both turning towards the axon and exclusion from dendrites depend on Kinesin-2, a plus-end-associated motor that guides growing plus ends along adjacent microtubules. We propose that Kinesin-2 engages with a polarised microtubule network within the soma to guide growing microtubules towards the axon; while at dendrite entry sites engagement with microtubules of opposite polarity generates a backward stalling force that prevents entry into dendrites and thus maintains minus-end-out polarity within proximal dendrites.
Highlights
Microtubules are polarised α/β-tubulin-based polymers essential for cell viability, providing pushing and pulling forces, structural support or tracks for the transport of intracellular cargo (Goodson and Jonasson, 2018). α-tubulin is located at the so-called minus end and β-tubulin is exposed at the so-called plus end, which is typically more dynamic
Knockdown of γ-tubulin ring complexes (γ-TuRCs) within model systems affects dynamic microtubules in all neuronal compartments (Nguyen et al, 2014; Ori-McKenney et al, 2012; Sánchez-Huertas et al, 2016; Yamada and Hayashi, 2019; Yau et al, 2014) and mutations in γ-TuRC genes have been linked to human neurodevelopmental disorders (Bahi-Buisson et al, 2014; Mitani et al, 2019; Poirier et al, 2013). γ-TuRCs are typically inactive until they are recruited to specific sites within cells, such as microtubule organising centres (MTOCs), the cytosol around mitotic chromatin, or the sides of pre-existing microtubules via binding to Augmin/HAUS complexes (Farache et al, 2018; Lin et al, 2014; Meunier and Vernos, 2016; Sanchez and Feldman, 2016; Teixidó-Travesa et al, 2012)
A range of MTOCs exist, including centrosomes, the Golgi apparatus and the nuclear envelope, and different cells use different MTOCs to help generate and organise their specific microtubule arrays (Sanchez and Feldman, 2016). γ-TuRC recruitment occurs via γTuRC “tethering proteins”, such as Drosophila Centrosomin (Cnn), that simultaneously bind to the γ-TuRC and a particular MTOC, and can help activate the γ-TuRC (Tovey and Conduit, 2018)
Summary
Microtubules are polarised α/β-tubulin-based polymers essential for cell viability, providing pushing and pulling forces, structural support or tracks for the transport of intracellular cargo (Goodson and Jonasson, 2018). α-tubulin is located at the so-called minus end and β-tubulin is exposed at the so-called plus end, which is typically more dynamic. Α-tubulin is located at the so-called minus end and β-tubulin is exposed at the so-called plus end, which is typically more dynamic This inherent microtubule polarity is important for cell polarity, as different motor proteins (Kinesins and Dynein) move cargo along microtubules in a specific direction – Dynein towards the minus end and most Kinesins towards the plus end. Most plus ends point away from the soma in axons (plus-end-out microtubules), while the microtubules in dendrites are either of mixed polarity or are predominantly minus-end-out (Hill et al, 2012; Kapitein and Hoogenraad, 2015; Kelliher et al, 2019; Tas et al, 2017) This difference between axons and dendrites is important for the correct distribution of cargo throughout the neuron (Harterink et al, 2018; Kapitein and Hoogenraad, 2015; Tas et al, 2017). A range of MTOCs exist, including centrosomes, the Golgi apparatus and the nuclear envelope, and different cells use different MTOCs to help generate and organise their specific microtubule arrays (Sanchez and Feldman, 2016). γ-TuRC recruitment occurs via γTuRC “tethering proteins”, such as Drosophila Centrosomin (Cnn), that simultaneously bind to the γ-TuRC and a particular MTOC, and can help activate the γ-TuRC (Tovey and Conduit, 2018)
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