Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity

He, Liu; Kooistra, Robbelien; Das, Ravi; Oudejans, Ellen; Leen, Eric van; Ziegler, Johannes; Portegies, Sybren; Haan, Bart de; Altena, Anna van Regteren; Stucchi, Riccardo; Altelaar, AF Maarten; Wieser, Stefan; Krieg, Michael; Hoogenraad, Casper C.; Harterink, Martin

doi:10.7554/elife.55111

Cited by 31 publications

(65 citation statements)

References 75 publications

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“…Instead, MTs are released from the dgMTOC, raising the question of how these MTs are subsequently stabilized. Recently, cortical anchoring of MTs through an Ankyrin-CRMP complex has been showed to immobilize MTs to regulate MT stability and polarity in mature dendrites ( He et al, 2020 ). Future studies will be needed to understand how this Ankyrin-CRMP-mediated anchoring mechanism functions together with the dgMTOC to create stable MTs in dendrites.…”

Section: Discussionmentioning

confidence: 99%

Growth cone-localized microtubule organizing center establishes microtubule orientation in dendrites

Liang

Kokes

Fetter

et al. 2020

eLife

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A polarized arrangement of neuronal microtubule arrays is the foundation of membrane trafficking and subcellular compartmentalization. Conserved among both invertebrates and vertebrates, axons contain exclusively 'plus-end-out' microtubules while dendrites contain a high percentage of 'minus-end-out' microtubules, the origins of which have been a mystery. Here we show that in Caenorhabditis elegans the dendritic growth cone contains a non-centrosomal microtubule organizing center, which generates minus-end-out microtubules along outgrowing dendrites and plus-end-out microtubules in the growth cone. RAB-11-positive endosomes accumulate in this region and co-migrate with the microtubule nucleation complex γ-TuRC. The MTOC tracks the extending growth cone by kinesin-1/UNC-116-mediated endosome movements on distal plus-end-out microtubules and dynein clusters this advancing MTOC. Critically, perturbation of the function or localization of the MTOC causes reversed microtubule polarity in dendrites. These findings unveil the endosome-localized dendritic MTOC as a critical organelle for establishing axon-dendrite polarity.

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Section: Discussionmentioning

confidence: 99%

Growth cone-localized microtubule organizing center establishes microtubule orientation in dendrites

Liang

Kokes

Fetter

et al. 2020

eLife

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“…To examine the subcellular localization of UNC-33, we expressed UNC-33L with GFP inserted between the globular domain and the C-terminal tail (UNC33L::internalGFP) with UNC-116-rigor::mCherry [ 36 ]. We found that UNC-33L::internalGFP formed a punctate pattern closely associated with microtubule bundles labelled by UNC-116-rigor::mCherry ( Fig 5G ).…”

Section: Resultsmentioning

confidence: 99%

“…How CRMP/UNC-33 brings these MT bundles together at the correct subcellular location and supports the axonal tracks specifically is a very interesting question. A very recent study demonstrated that MTs in PVDs are anchored to the cell cortex by linking MT-associated CRMP/UNC-33 and the membrane-associated Ankyrin/UNC-44 via UNC-119 [ 36 ]. The membrane-associated complex acts as a pin to anchor MTs in a regular interval to the cell cortex, which is consistent to the working model in this study ( Fig 7 ).…”

Section: Discussionmentioning

confidence: 99%

“…The motor rigor mutation sites are at the ATP-binding motif for motors to bind MTs without dissociation as described [ 25 , 57 ]. To express functional UNC-33L::internalGFP, we inserted GFP into unc-33 gene at the start of S isoform to generate pYC26 as previously described [ 36 ]. To visualize F-actin in PVD, we expressed Pser2prom3 :: tag :: RFP :: UtrCH , which is a gift form Hannes E Bűlow lab.…”

Section: Methodsmentioning

confidence: 99%

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CRMP/UNC-33 organizes microtubule bundles for KIF5-mediated mitochondrial distribution to axon

et al. 2021

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Neurons are highly specialized cells with polarized cellular processes and subcellular domains. As vital organelles for neuronal functions, mitochondria are distributed by microtubule-based transport systems. Although the essential components of mitochondrial transport including motors and cargo adaptors are identified, it is less clear how mitochondrial distribution among somato-dendritic and axonal compartment is regulated. Here, we systematically study mitochondrial motors, including four kinesins, KIF5, KIF17, KIF1, KLP-6, and dynein, and transport regulators in C. elegans PVD neurons. Among all these motors, we found that mitochondrial export from soma to neurites is mainly mediated by KIF5/UNC-116. Interestingly, UNC-116 is especially important for axonal mitochondria, while dynein removes mitochondria from all plus-end dendrites and the axon. We surprisingly found one mitochondrial transport regulator for minus-end dendritic compartment, TRAK-1, and two mitochondrial transport regulators for axonal compartment, CRMP/UNC-33 and JIP3/UNC-16. While JIP3/UNC-16 suppresses axonal mitochondria, CRMP/UNC-33 is critical for axonal mitochondria; nearly no axonal mitochondria present in unc-33 mutants. We showed that UNC-33 is essential for organizing the population of UNC-116-associated microtubule bundles, which are tracks for mitochondrial trafficking. Disarrangement of these tracks impedes mitochondrial transport to the axon. In summary, we identified a compartment-specific transport regulation of mitochondria by UNC-33 through organizing microtubule tracks for different kinesin motors other than microtubule polarity.

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“…Based on our data on UNC119-mediated trafficking of LCK to the IS [79], we speculate that UNC119 could aid LCK lateral diffusion at the plasma membrane and overcome diffusion barriers by relocating LCK between membrane compartments (e.g., from non-IS to IS). A recent study showed that UNC119 forms a complex with Uncoordinated (UNC)-44 (ankyrin) and UNC-33 (or CRMP) in C. elegans' primary neurons [135], linking UNC119 with the cortical actin, which would support a potential role for UNC119 in translocating molecules across membrane domains.…”

Section: Dynamic Behavior Of Molecules At the Immunological Synapse: mentioning

confidence: 99%

Spatiotemporal Regulation of Signaling: Focus on T Cell Activation and the Immunological Synapse

García¹,

Ismail²

2020

IJMS

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In a signaling network, not only the functions of molecules are important but when (temporal) and where (spatial) those functions are exerted and orchestrated is what defines the signaling output. To temporally and spatially modulate signaling events, cells generate specialized functional domains with variable lifetime and size that concentrate signaling molecules, enhancing their transduction potential. The plasma membrane is a key in this regulation, as it constitutes a primary signaling hub that integrates signals within and across the membrane. Here, we examine some of the mechanisms that cells exhibit to spatiotemporally regulate signal transduction, focusing on the early events of T cell activation from triggering of T cell receptor to formation and maturation of the immunological synapse.

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Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity

Cited by 31 publications

References 75 publications

Growth cone-localized microtubule organizing center establishes microtubule orientation in dendrites

Growth cone-localized microtubule organizing center establishes microtubule orientation in dendrites

CRMP/UNC-33 organizes microtubule bundles for KIF5-mediated mitochondrial distribution to axon

Spatiotemporal Regulation of Signaling: Focus on T Cell Activation and the Immunological Synapse

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