Severing enzymes amplify microtubule arrays through lattice GTP-tubulin incorporation

Vemu, Annapurna; Szczęsna, Ewa; Zehr, Elena A.; Spector, Jeffrey O.; Grigorieff, Nikolaus; Deaconescu, Alexandra M.; Roll-Mecak, Antonina

doi:10.1126/science.aau1504

Cited by 196 publications

(241 citation statements)

References 68 publications

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“…This is likely because parallel pathways can be used to generate new minus ends. For example, microtubule severing can be used to generate new plus and minus ends and amplify microtubule number [44,73]. In many cell types, minus ends generated when a microtubule is severed are recognized by minus-end binding proteins in the calmodulin-regulated spectrin-associated protein (CAM-SAP)/Patronin family [74,75].…”

Section: Discussionmentioning

confidence: 99%

“…Although γTub plays a role in controlling microtubule nucleation and polarity in ddaE neurons, even strong reduction of function does not affect overall shape of these cells [26], perhaps because, under normal conditions, amplification of microtubule number through severing [44] can compensate for reduced nucleation. In larger ddaC neurons, dendrite simplification is seen when γTub is reduced [25].…”

Section: A Subset Of Canonical Wnt Signaling Proteins Is Required Formentioning

confidence: 99%

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Endosomal Wnt signaling proteins control microtubule nucleation in dendrites

et al. 2020

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Dendrite microtubules are polarized with minus-end-out orientation in Drosophila neurons. Nucleation sites concentrate at dendrite branch points, but how they localize is not known. Using Drosophila, we found that canonical Wnt signaling proteins regulate localization of the core nucleation protein γTubulin (γTub). Reduction of frizzleds (fz), arrow (low-density lipoprotein receptor-related protein [LRP] 5/6), dishevelled (dsh), casein kinase Iγ, G proteins, and Axin reduced γTub-green fluorescent protein (GFP) at branch points, and two functional readouts of dendritic nucleation confirmed a role for Wnt signaling proteins. Both dsh and Axin localized to branch points, with dsh upstream of Axin. Moreover, tethering Axin to mitochondria was sufficient to recruit ectopic γTub-GFP and increase microtubule dynamics in dendrites. At dendrite branch points, Axin and dsh colocalized with early endosomal marker Rab5, and new microtubule growth initiated at puncta marked with fz, dsh, Axin, and Rab5. We propose that in dendrites, canonical Wnt signaling proteins are housed on early endosomes and recruit nucleation sites to branch points. OPEN ACCESS Citation: Weiner AT, Seebold DY, Torres-Gutierrez P, Folker C, Swope RD, Kothe GO, et al. (2020) Endosomal Wnt signaling proteins control microtubule nucleation in dendrites. PLoS Biol 18 (3): e3000647. https://doi.

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Section: Discussionmentioning

confidence: 99%

Section: A Subset Of Canonical Wnt Signaling Proteins Is Required Formentioning

confidence: 99%

Endosomal Wnt signaling proteins control microtubule nucleation in dendrites

et al. 2020

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“…occurrence of GTP-islands (Vemu et al, 2018;Kuo et al, 2019). To what extent CLIP-170 is implicated in these processes still remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Stress-induced phosphorylation of CLIP-170 by JNK promotes microtubule rescue

Henrie

Bakhos-Douaihy

Cantaloube

et al. 2020

Journal of Cell Biology

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The stress-induced c-Jun N-terminal kinase (JNK) controls microtubule dynamics by enhancing both microtubule growth and rescues. Here, we show that upon cell stress, JNK directly phosphorylates the microtubule rescue factor CLIP-170 in its microtubule-binding domain to increase its rescue-promoting activity. Phosphomimetic versions of CLIP-170 enhance its ability to promote rescue events in vitro and in cells. Furthermore, while phosphomimetic mutations do not alter CLIP-170’s capability to form comets at growing microtubule ends, both phosphomimetic mutations and JNK activation increase the occurrence of CLIP-170 remnants on the microtubule lattice at the rear of comets. As the CLIP-170 remnants, which are potential sites of microtubule rescue, display a shorter lifetime when CLIP-170 is phosphorylated, we propose that instead of acting at the time of rescue occurrence, CLIP-170 would rather contribute in preparing the microtubule lattice for future rescues at these predetermined sites.

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“…However, recent studies indicate that GTP-bound tubulin dimers are also present further along the microtubule lattice 15,16 . These so-called GTP-tubulin islands could serve as rescue sites to prevent depolymerization of the microtubule or provide a location for selfrepair [16][17][18][19][20] .…”

Section: Introductionmentioning

confidence: 99%

Nano-positioning and tubuline conformation determine transport of mitochondria along microtubules

Steenbergen

Lavoie-Cardinal

Kazwiny³

et al. 2020

Preprint

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Correct spatiotemporal distribution of organelles and vesicles is crucial for healthy cell functioning and is regulated by intracellular transport mechanisms. Controlled transport of bulky mitochondria is especially important in polarized cells such as neurons that rely on these organelles to locally produce energy and buffer calcium.Mitochondrial transport requires and depends on microtubules which fill much of the available axonal space. How mitochondrial transport is affected by their position within the microtubule bundles is not known. Here, we found that anterograde transport, driven by kinesin motors, is susceptible to the molecular conformation of tubulin both in vitro and in vivo. Anterograde velocities negatively correlate with the density of elongated tubulin dimers, similar to GTP-tubulin, that are more straight and rigid. The impact of the tubulin conformation depends primarily on where a mitochondrion is positioned, either within or at the rim of microtubule bundle. Increasing elongated tubulin levels lowers the number of motile anterograde mitochondria within the microtubule bundle and increases anterograde transport speed at the microtubule bundle rim. We demonstrate that the increased kinesin step processivity on microtubules consisting of elongated dimers underlies increased mitochondrial dynamics. Our work indicates that the molecular conformation of tubulin controls mitochondrial motility and as such locally regulates the distribution of mitochondria along axons.

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Severing enzymes amplify microtubule arrays through lattice GTP-tubulin incorporation

Cited by 196 publications

References 68 publications

Endosomal Wnt signaling proteins control microtubule nucleation in dendrites

Endosomal Wnt signaling proteins control microtubule nucleation in dendrites

Stress-induced phosphorylation of CLIP-170 by JNK promotes microtubule rescue

Nano-positioning and tubuline conformation determine transport of mitochondria along microtubules

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