Wnt signaling establishes the microtubule polarity in neurons through regulation of Kinesin-13

Puri, Dharmendra; Ponniah, Keerthana; Basu, Atrayee; Dey, Swagata; Lundquist, Erik A.; Ghosh-Roy, Anindya

doi:10.1083/jcb.202005080

Cited by 18 publications

(33 citation statements)

References 88 publications

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“…We determined the polarity of the microtubules from the direction of microtubule growth from the plus ends, as seen in the kymographs (Figure 3B) from the regions of interest in the anterior and posterior processes of PLM neuron (Figure 3A). In the wild-type background, the PLM anterior process had the majority of the EBP-2::GFP movements away from the cell body (plus-end-out, green trace), while in the posterior process, EBP-2::GFP movements were seen both away from and towards the cell body (minus-end-out, magenta trace, Figure 3A-B), as reported before (7). We plotted the fraction of microtubule tracks with ‘plus-end-out’ or ‘minus-end-out’ orientation (Figure 3C).…”

Section: Resultssupporting

confidence: 81%

“…Additionally, PLM also has a short posterior process (double-sided white arrow, Figure 1A). Recently, we showed that loss of kinesin-13/KLP-7 microtubule depolymerizing protein, leads to multiple axon-like phenotype in ALM neuron (orange arrow, Figure 1A), and the overgrowth phenotype of the PLM posterior process (double-sided white arrow, Figure1A),Figure 1A) due to excessive stabilization of the microtubule cytoskeleton (7). Destabilization of microtubules using colchicine or loss of tubulin subunits suppresses the axon overgrowth phenotype seen in the klp-7 mutant (7).…”

Section: Resultsmentioning

confidence: 99%

“…There are many reports which suggest that this structural and functional polarity of neurons is a function of cytoskeletal elements within the neuron (1-4). The cytoskeletal elements are regulated by intra- and extra-cellular signal transduction pathways during neuronal polarization (5-7). The organization of cytoskeletal component, microtubules, in the neuron, directs neuronal polarization, and development (8).…”

Section: Introductionmentioning

confidence: 99%

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Musleblind-1 regulates microtubule cytoskeleton in C. elegans mechanosensory neuron through tubulin mRNAs

Puri

Samaddar

Banerjee

et al. 2022

Preprint

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Regulation of microtubule cytoskeleton is fundamental for the development and maintenance of neuronal architecture. Recent studies have shown that regulated RNA processing is also critical for the establishment and maintenance of neural circuits. In a genetic screen using mechanosensory neurons of C. elegans, we identified a mutation in muscleblind-1 as a suppressor of loss of kinesin-13 family microtubule destabilizing factor klp-7. Muscleblind-1(MBL-1) is an RNA-binding protein that regulates the splicing, localization, and stability of RNA. We found that mbl-1 is required cell-autonomously for axon growth and synapse formation in the posterior lateral microtubule (PLM) neuron. Loss of mbl-1 affects stability and plus-end-out organization of microtubules in the anterior process of PLM. These defects are also accompanied by abnormal axonal transport of the synaptic protein RAB-3 and loss of gentle touch sensation in mbl-1 mutant. Our data showed that mbl-1 is genetically epistatic to mec-7 (β-tubulin) and mec-12 (α-tubulin) for axon growth. The immunoprecipitation of MBL-1 pulls down the mec-7, mec-12, and sad-1 mRNAs. Additionally, the mbl-1 mutants show a reduction in the level and stability of mec-7 and mec-12 transcripts. Independently, mbl-1 is epistatic to sad-1 for synapse formation. Our work elucidated a previously unknown link between RNA binding protein and cytoskeletal machinery for the development and maintenance of the nervous system.

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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Musleblind-1 regulates microtubule cytoskeleton in C. elegans mechanosensory neuron through tubulin mRNAs

Puri

Samaddar

Banerjee

et al. 2022

Preprint

Self Cite

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“…We observed the development of two mechanosensory neurons, anterior lateral mechanosensory (ALM) and posterior lateral mechanosensory (PLM) neurons ( Figure 1C ) because the tiling between PLM and ALM neurons are strictly regulated by microtubule regulating factors, such as kinesin-13. Previous studies have shown worm mutants with more stable microtubules have defects in tiling between PLM and ALM ( Puri et al, 2021 ). In wild-type animals, the axonal tip of PLM neurons does not reach the cell body of ALM without overlapping with each other (wild-type in Figure 1D and E ; Gallegos and Bargmann, 2004 ).…”

Section: Resultsmentioning

confidence: 99%

Structural model of microtubule dynamics inhibition by kinesin-4 from the crystal structure of KLP-12 –tubulin complex

Taguchi

Nakano

Imasaki

et al. 2022

eLife

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Kinesin superfamily proteins are microtubule-based molecular motors driven by the energy of ATP hydrolysis. Among them, the kinesin-4 family is a unique motor that inhibits microtubule dynamics. Although mutations of kinesin-4 cause several diseases, its molecular mechanism is unclear because of the difficulty of visualizing the high-resolution structure of kinesin-4 working at the microtubule plus-end. Here, we report that KLP-12, a C. elegans kinesin-4 ortholog of KIF21A and KIF21B, is essential for proper length control of C. elegans axons, and its motor domain represses microtubule polymerization in vitro. The crystal structure of the KLP-12 motor domain complexed with tubulin, which represents the high-resolution structural snapshot of the inhibition state of microtubule-end dynamics, revealed the bending effect of KLP-12 for tubulin. Comparison with the KIF5B-tubulin and KIF2C-tubulin complexes, which represent the elongation and shrinking forms of microtubule ends, respectively, showed the curvature of tubulin introduced by KLP-12 is in between them. Taken together, KLP-12 controls the proper length of axons by modulating the curvature of the microtubule ends to inhibit the microtubule dynamics.

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“… Weiner et al (2020) showed that in Drosophila , some Wnt signaling proteins, such as Fz, LRP5/6 or Axin, recruit the MT core-nucleation protein γ-Tubulin to endosomes in the dendritic branch points, enabling local MT nucleation and indicating that extracellular Wnt signaling can regulate local MT nucleation in dendrites. In addition, two other recent studies have revealed that the Wnt pathway controls axon specification in developing neurons by organizing the polarity of MT networks both in the axon ( Stanganello et al, 2019 ) and in non-axonal neurites ( Puri et al, 2021 ). Plus, it is known that local MT nucleation contribute the MT arrangements in these compartments ( Sánchez-Huertas et al, 2016 ; Cunha-Ferreira et al, 2018 ).…”

Section: Microtubule-associated Proteins In Axon Guidancementioning

confidence: 99%

With the Permission of Microtubules: An Updated Overview on Microtubule Function During Axon Pathfinding

Sánchez-Huertas

Herrera

2021

Front. Mol. Neurosci.

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During the establishment of neural circuitry axons often need to cover long distances to reach remote targets. The stereotyped navigation of these axons defines the connectivity between brain regions and cellular subtypes. This chemotrophic guidance process mostly relies on the spatio-temporal expression patterns of extracellular proteins and the selective expression of their receptors in projection neurons. Axon guidance is stimulated by guidance proteins and implemented by neuronal traction forces at the growth cones, which engage local cytoskeleton regulators and cell adhesion proteins. Different layers of guidance signaling regulation, such as the cleavage and processing of receptors, the expression of co-receptors and a wide variety of intracellular cascades downstream of receptors activation, have been progressively unveiled. Also, in the last decades, the regulation of microtubule (MT) assembly, stability and interactions with the submembranous actin network in the growth cone have emerged as crucial effector mechanisms in axon pathfinding. In this review, we will delve into the intracellular signaling cascades downstream of guidance receptors that converge on the MT cytoskeleton of the growing axon. In particular, we will focus on the microtubule-associated proteins (MAPs) network responsible of MT dynamics in the axon and growth cone. Complementarily, we will discuss new evidences that connect defects in MT scaffold proteins, MAPs or MT-based motors and axon misrouting during brain development.

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Wnt signaling establishes the microtubule polarity in neurons through regulation of Kinesin-13

Cited by 18 publications

References 88 publications

Musleblind-1 regulates microtubule cytoskeleton in C. elegans mechanosensory neuron through tubulin mRNAs

Musleblind-1 regulates microtubule cytoskeleton in C. elegans mechanosensory neuron through tubulin mRNAs

Structural model of microtubule dynamics inhibition by kinesin-4 from the crystal structure of KLP-12 –tubulin complex

With the Permission of Microtubules: An Updated Overview on Microtubule Function During Axon Pathfinding

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