Microtubule nucleation and organization in dendrites

Delandre, Caroline; Amikura, Reiko; Moore, Adrian W.

doi:10.1080/15384101.2016.1172158

Cited by 36 publications

(32 citation statements)

References 88 publications

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“…The analysis indicated that the method performs well at a range of <15 MTs/pixel, after which it fails to extract correct parameters. This provides a rough estimate as to which neurons, besides C. elegans motor neuron, the method can be used for (Bray and Bunge, 1981; Burton, 1987; Chalfie and Thomson, 1982; Delandre et al, 2016; Yu and Baas, 1994). …”

Section: Resultsmentioning

confidence: 99%

Microtubule Organization Determines Axonal Transport Dynamics

Yogev

Cooper

Fetter

et al. 2016

Neuron

123

138

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Axonal microtubule (MT) arrays are the major cytoskeleton substrate for cargo transport. How MT organization, i.e. polymer length, number and minus-end spacing is regulated, and how it impinges on axonal transport is unclear. We describe a method for analyzing neuronal MT organization using light microscopy. This method circumvents the need for electron microscopy reconstructions and is compatible with live imaging of cargo transport and MT dynamics. Examination of a C. elegans motor neuron revealed how age, MT associated proteins and signaling pathways control MT length, minus-end spacing and coverage. In turn, MT organization determines axonal transport progression: cargoes pause at polymer termini, suggestive that switching MT tracks is rate limiting for efficient transport. Cargo run length is set by MT length, and higher MT coverage correlates with shorter pauses. These results uncover the principles and mechanisms of neuronal MT organization and its regulation of axonal cargo transport.

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Section: Resultsmentioning

confidence: 99%

Microtubule Organization Determines Axonal Transport Dynamics

Yogev

Cooper

Fetter

et al. 2016

Neuron

123

138

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“…One possibility is that local MT nucleation events occur in dendrites, via gamma-tubulin and Golgi outposts that introduce minus-end-out MTs (Nguyen et al, 2014, Delandre et al, 2016). This is probably not the primary mechanism, however, because the presence of Golgi elements in dendrites requires that at least some minus-end-out MTs are already present (Baas et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic Dynein Transports Axonal Microtubules in a Polarity-Sorting Manner

Rao¹,

Patil²,

Black³

et al. 2017

Cell Reports

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Summary Axonal microtubules are predominantly organized into a plus-end-out pattern.Here, we examined the polarity-sorting mechanism underlying this organization both experimentally and using modeling. The posited mechanism centers on cytoplasmic dynein transporting plus-end-out and minus-end-out microtubules into and out of the axon, respectively. When cytoplasmic dynein was acutely inhibited, the bi-directional transport of microtubules in the axon was disrupted in both directions, after which minus-end-out microtubules accumulated in the axon over time. Computational modeling revealed that dynein-mediated transport of microtubules can establish and preserve a predominantly plus-end-out microtubule pattern as per the details of the experimental findings, but only if a kinesin motor and a static cross-linker protein are also at play. Consistent with the predictions of the model, partial depletion of TRIM46, a protein that cross-links axonal microtubules in a manner that influences their polarity orientation, leads to an increase in microtubule transport.

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“…Microtubule polarity, however, varies within the dendritic arbors of da neurons (Stone et al, 2008), and it is possible that Golgi outposts are nevertheless sufficient to locally influence microtubule polarity as previously reported (Delandre et al, 2016;Ori-McKenney et al, 2012;Yalgin et al, 2015). To test the idea that outposts have the capacity to affect microtubule polarity, we used a paradigm in which Golgi outposts are ectopically localized to axons, a compartment from which outposts are normally excluded and in which microtubules are uniformly oriented with their plus-ends distal.…”

Section: Loss Of Gm130 Significantly Reduces Misoriented Microtubulesmentioning

confidence: 99%

“…In studies using fluorescently tagged End-binding 1 (EB1::GFP), which marks growing microtubule ends, Golgi outposts have been shown to correlate with microtubule growth initiation sites in developing dendrites (Ori-McKenney et al, 2012;Yalgin et al, 2015;Zhou et al, 2014). This correlation has led to the model that Golgi outposts function as MTOCs that support acentrosomal nucleation and the directional growth of microtubules during dendrite branch formation (Delandre et al, 2016). Decreasing the levels of proteins involved in microtubule nucleation, such as γ-tubulin and its interactors centrosomin (cnn, the fly ortholog of CDK5RAP2) and pericentrin-like protein (plp, the Drosophila ortholog of AKAP450), disrupts the correlation between microtubule growth initiation sites and outposts and perturbs dendrite branch growth (Ori-McKenney et al, 2012;Yalgin et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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

Yang

Wildonger

2019

Preprint

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ABSTRACTMicrotubule-organizing centers (MTOCs) often play a central role in organizing the cellular microtubule networks that underlie cell function. In neurons, microtubules in axons and dendrites have distinct polarities. Dendrite-specific Golgi outposts, in particular multi-compartment outposts, have emerged as regulators of acentrosomal microtubule growth, raising the question of whether outposts contribute to establishing the overall polarity of the dendritic microtubule cytoskeleton. The cis-Golgi matrix protein GM130 has roles in both the MTOC activity of Golgi and in connecting Golgi compartments to form multi-compartment units. Using a combination of genetic approaches and live imaging in a Drosophila model, we found that GM130 is not essential for the overall polarity of the dendritic microtubule cytoskeleton. However, the mislocalization of multi-compartment Golgi outposts to axons disrupts the uniform orientation of axonal microtubules. This suggests that outposts have the capacity to influence microtubule polarity and, as our data indicate, likely do so independently of microtubule nucleation mediated by the γ-tubulin ring complex (γ-TuRC). Altogether, our results are consistent with the model that multi-compartment Golgi outposts may locally influence microtubule polarity, but that outposts are not necessary for the overall polarity of the dendritic microtubule cytoskeleton.

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Microtubule nucleation and organization in dendrites

Cited by 36 publications

References 88 publications

Microtubule Organization Determines Axonal Transport Dynamics

Microtubule Organization Determines Axonal Transport Dynamics

Cytoplasmic Dynein Transports Axonal Microtubules in a Polarity-Sorting Manner

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

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