Golgi outposts locally regulate microtubule orientation in neurons but are not required for the overall polarity of the dendritic cytoskeleton

Yang, Sihui; Wildonger, Jill

doi:10.1101/866574

Cited by 4 publications

(2 citation statements)

References 67 publications

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“…However, in a subsequent study Cnn, which cooperates with Plp and has a wellknown role as recruitment and activation factor for γ-tubulin at centrosomes, was also observed at branch points, in close proximity with Golgi outposts, and promoted nucleation of minus-end-out microtubules at this site (Yalgin et al, 2015). More recent work found no effect of Golgi outposts on overall microtubule polarity in dendrites, but suggested that Golgi outposts may locally modulate microtubule organization in a γTuRC-independent manner (Yang & Wildonger, 2019). Summarizing these somewhat contradictory results, dendritic branch points seem to be preferred sites of γ-tubulin recruitment and nucleation, involving proteins that also assemble the centrosomal MTOC, but whether Golgi outposts are the MTOC-harboring structure that controls dendritic microtubule polarity or whether a different, yet to be identified organelle/ structure is involved, requires further analysis.…”

Section: In Search Of a Non-centrosomal Mtocmentioning

confidence: 86%

Nucleating microtubules in neurons: Challenges and solutions

Lüders

2020

Developmental Neurobiology

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The highly polarized morphology of neurons is crucial for their function and involves formation of two distinct types of cellular extensions, the axonal and dendritic compartments. An important effector required for the morphogenesis and maintenance and thus the identity of axons and dendrites is the microtubule cytoskeleton. F I G U R E 1The non-centrosomal microtubule network in neurons. Comparison of the non-centrosomal organization of the microtubule network in neurons (top) with the centrosome-based array typically found in cycling cells (bottom). Microtubules are displayed in different colors, depending on their polarity. Microtubule polarity is also indicated by a plus or minus symbol at the end that is facing the cell periphery. Axons contain almost exclusively plus-end-out microtubules, whereas dendrites contain microtubules of mixed polarity. Mixed polarity refers to bundles of microtubules rather than individual microtubules (see configuration in magnified dendrite region). Centrioles are present but have lost MTOC activity. In contrast, in cycling cells centrioles form an active MTOC, the centrosome, which is at the center of the microtubule network. In some cells the Golgi, positioned in close proximity to the centrosome, may contribute to the overall radial organization of microtubules, which have their minus-ends anchored at the MTOC and extend their plus-ends toward the periphery How to cite this article: Lüders J. Nucleating microtubules in neurons: Challenges and solutions.

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Section: In Search Of a Non-centrosomal Mtocmentioning

confidence: 86%

Nucleating microtubules in neurons: Challenges and solutions

Lüders

2020

Developmental Neurobiology

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“…The microtubules in the primary protrusion of qNSCs are predominantly acentrosomal; the qNSCs in newly hatched larvae possess inactive centrosomes, which mature over time during NSC reactivation 33 . Although Golgi has emerged as potential acentrosomal MTOCs in several cell types 43,52,65–67 , the role of Golgi in acentrosomal microtubule growth in qNSC was unknown. We have revealed that Golgi are present as 1-3 punctate structures at the PIS and pericentrosomal regions, as compared to the scattered distribution of smaller Golgi puncta in the cytosol and perinuclear region of dividing NSCs.…”

Section: Discussionmentioning

confidence: 99%

Golgi-dependent Reactivation and Regeneration of Quiescent Neural Stem Cells

Gujar

Gao

Teng³

et al. 2022

Preprint

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The ability of stem cells to switch between quiescent and proliferative states is crucial for maintaining tissue homeostasis and regeneration. In Drosophila, quiescent neural stem cells (qNSCs) extend a primary protrusion, which is removed prior to NSC reactivation. Here, we have unravelled that qNSC protrusions can be regenerated upon injury. This regeneration process relies on the Golgi apparatus which acts as the major acentrosomal microtubule-organizing centre in qNSCs. A Golgi-resident GTPase Arf1 and its guanine-nucleotide exchange factor Sec71 promote NSC reactivation and regeneration via the regulation of microtubule growth. Arf1 physically associates with its new effector Mini Spindles (Msps)/XMAP215, a microtubule polymerase. Finally, Arf1 functions upstream of Msps to target the cell-adhesion molecule E-cadherin to NSC-neuropil contact sites during NSC reactivation. Our findings have established Drosophila qNSCs as a new regeneration model and identified a novel Arf1/Sec71-Msps pathway in the regulation of microtubule growth and NSC reactivation.

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Microtubules originate asymmetrically at the somatic Golgi and are guided via Kinesin2 to maintain polarity within neurons

Mukherjee

Brooks

Bernard

et al. 2019

Preprint

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Microtubules form polarised arrays throughout axons and dendrites necessary for neuronal growth and maintenance. γ-tubulin-ring-complexes (γ-TuRCs) nucleate microtubules at microtubule organising centres (MTOCs), but how microtubules are generated and organised within neurons remains unclear. We show that γ-TuRCs are predominantly recruited to the somatic Golgi, rather than to dendritic Golgi outposts, within Drosophila neurons. Microtubules nucleated from the somatic Golgi grow preferentially towards and into the axon, while growing microtubules that approach dendrites are excluded. Both directed growth and dendritic exclusion depend upon Kinesin-2, which associates with plus ends and directs their growth towards the plus ends of adjacent microtubules. We propose that plus-end-associated Kinesin-2 guides growing microtubules nucleated from the somatic Golgi towards the axon and prevents plus end entry into dendrites when engaging with oppositely polarised microtubules.In summary, microtubules are nucleated from the somatic Golgi within neurons and their guidance is necessary to maintain neuronal microtubule polarity. envelope, and different cells use different MTOCs to help generate and organise their specific microtubule arrays 18 . γ-TuRC recruitment occurs via γ-TuRC "tethering proteins" that simultaneously bind to the MTOC and γ-TuRC, possibly also helping to activate the γ-TuRC. An example is Drosophila Centrosomin (Cnn) and its mammalian homologue CDK5RAP2, which recruit γ-TuRCs to centrosomes during mitosis [23][24][25][26] and whose binding can activate γ-TuRCs 27-29 . γ-TuRCs can be recruited to different MTOCs by different tethering proteins, and it was also recently shown that different isoforms of Cnn can mediate recruitment to different MTOCs 29 . Thus, there is potentially a wide-range of γ-TuRC recruitment mechanisms available and understanding which mechanisms are used in different cells, including neurons, remains poorly understood.Although it is known that γ-tubulin is important 10-14 , it remains unclear how microtubule nucleation is regulated within neurons. During early development of mammalian neurons, the centrosome within the soma nucleates microtubules 30 that are severed and transported into neurites via motor-based microtubule sliding 31 . Microtubules sliding is also important for axon outgrowth in Drosophila cultured neurons 32,33 , and for establishing microtubule polarity [34][35][36][37][38] . Centrosomes are inactivated, however, at later developmental stages 30 and are dispensable for neuronal development in both mammalian and fly neurons 30,39 . No other active MTOCs within the neuronal soma have been described. Nevertheless, microtubules continue to grow within the soma 11,39 , and in mammalian neurons this depends in part on HAUS 11 , which is also important for microtubule growth within axons and dendrites 11,40 . Some MTOCs have been identified within dendrites in different neurons. For example, the basal body, or its surrounding region, within C. elegans ciliated neurons a...

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Golgi outposts locally regulate microtubule orientation in neurons but are not required for the overall polarity of the dendritic cytoskeleton

Cited by 4 publications

References 67 publications

Nucleating microtubules in neurons: Challenges and solutions

Nucleating microtubules in neurons: Challenges and solutions

Golgi-dependent Reactivation and Regeneration of Quiescent Neural Stem Cells

Microtubules originate asymmetrically at the somatic Golgi and are guided via Kinesin2 to maintain polarity within neurons

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