Cortical Anchoring of the Microtubule Cytoskeleton is Essential for Neuron Polarity

Overview

Journal Elife

Specialty Biology

Date 2020 Apr 16

PMID 32293562

Citations 24

Authors

Liu He

Robbelien Kooistra

Ravi Das

Ellen Oudejans

Eric van Leen

Johannes Ziegler

Sybren Portegies

Bart De Haan

Anna van Regteren Altena

Riccardo Stucchi

Af Maarten Altelaar

Stefan Wieser

Michael Krieg

Casper C Hoogenraad

Martin Harterink

Affiliations

Soon will be listed here.

Abstract

The development of a polarized neuron relies on the selective transport of proteins to axons and dendrites. Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is poorly understood. Using the in vivo model system , we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubule-associated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cortex. This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals.

Citing Articles

Axonal Mechanotransduction Drives Cytoskeletal Responses to Physiological Mechanical Forces.

Swaim G, Glomb O, Xie Y, Emerson C, Li Z, Beaudet D bioRxiv. 2025; .

PMID: 39990487 PMC: 11844441. DOI: 10.1101/2025.02.11.637689.

Multimodal Characterization of Cortical Neuron Response to Permanent Magnetic Field Induced Nanomagnetic Force Maps.

Beck C, Kirby A, Roberts S, Kunze A ACS Nano. 2024; 18(51):34630-34645.

PMID: 39654337 PMC: 11674720. DOI: 10.1021/acsnano.4c09542.

The kinetochore protein KNL-1 regulates the actin cytoskeleton to control dendrite branching.

Alves Domingos H, Green M, Ouzounidis V, Finlayson C, Prevo B, Cheerambathur D J Cell Biol. 2024; 224(2).

PMID: 39625434 PMC: 11613958. DOI: 10.1083/jcb.202311147.

Parallelized Mechanical Stimulation of Neuronal Calcium Through Cell-Internal Nanomagnetic Forces Provokes Lasting Shifts in the Network Activity State.

Beck C, Kunze A Small. 2024; 21(1):e2406678.

PMID: 39460486 PMC: 11812431. DOI: 10.1002/smll.202406678.

KLP-7/Kinesin-13 orchestrates axon-dendrite checkpoints for polarized trafficking in neurons.

Dey S, Kumar N, Balakrishnan S, Koushika S, Ghosh-Roy A Mol Biol Cell. 2024; 35(9):ar115.

PMID: 38985513 PMC: 7616348. DOI: 10.1091/mbc.E23-08-0335.

References

Leterrier C, Vacher H, Fache M, Angles dOrtoli S, Castets F, Autillo-Touati A . End-binding proteins EB3 and EB1 link microtubules to ankyrin G in the axon initial segment. Proc Natl Acad Sci U S A. 2011; 108(21):8826-31. PMC: 3102358. DOI: 10.1073/pnas.1018671108. View

Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Janet Huang Y . UNC119 is required for G protein trafficking in sensory neurons. Nat Neurosci. 2011; 14(7):874-80. PMC: 3178889. DOI: 10.1038/nn.2835. View

Mokhtar S, Kim M, Magee K, Aui P, Thomas S, Bakhuraysah M . Amyloid-beta-dependent phosphorylation of collapsin response mediator protein-2 dissociates kinesin in Alzheimer's disease. Neural Regen Res. 2018; 13(6):1066-1080. PMC: 6022475. DOI: 10.4103/1673-5374.233451. View

Knobel K, Davis W, Jorgensen E, Bastiani M . UNC-119 suppresses axon branching in C. elegans. Development. 2001; 128(20):4079-92. DOI: 10.1242/dev.128.20.4079. View

Patterson G, Lippincott-Schwartz J . A photoactivatable GFP for selective photolabeling of proteins and cells. Science. 2002; 297(5588):1873-7. DOI: 10.1126/science.1074952. View

Chen F, Chisholm A, Jin Y . Tissue-specific regulation of alternative polyadenylation represses expression of a neuronal ankyrin isoform in epidermal development. Development. 2017; 144(4):698-707. PMC: 5312038. DOI: 10.1242/dev.146001. View

Sanchez-Soriano N, Travis M, Dajas-Bailador F, Goncalves-Pimentel C, Whitmarsh A, Prokop A . Mouse ACF7 and drosophila short stop modulate filopodia formation and microtubule organisation during neuronal growth. J Cell Sci. 2009; 122(Pt 14):2534-42. PMC: 2704885. DOI: 10.1242/jcs.046268. View

Krieg M, Stuhmer J, Cueva J, Fetter R, Spilker K, Cremers D . Genetic defects in β-spectrin and tau sensitize axons to movement-induced damage via torque-tension coupling. Elife. 2017; 6. PMC: 5298879. DOI: 10.7554/eLife.20172. View

Muller M, Monkemoller V, Hennig S, Hubner W, Huser T . Open-source image reconstruction of super-resolution structured illumination microscopy data in ImageJ. Nat Commun. 2016; 7:10980. PMC: 4802170. DOI: 10.1038/ncomms10980. View

10.

Otsuka A, Boontrakulpoontawee P, Rebeiz N, Domanus M, Otsuka D, Velamparampil N . Novel UNC-44 AO13 ankyrin is required for axonal guidance in C. elegans, contains six highly repetitive STEP blocks separated by seven potential transmembrane domains, and is localized to neuronal processes and the periphery of neural cell bodies. J Neurobiol. 2002; 50(4):333-49. DOI: 10.1002/neu.10036. View

11.

Rumpf S, Wolterhoff N, Herzmann S . Functions of Microtubule Disassembly during Neurite Pruning. Trends Cell Biol. 2019; 29(4):291-297. DOI: 10.1016/j.tcb.2019.01.002. View

12.

Freal A, Fassier C, Le Bras B, Bullier E, De Gois S, Hazan J . Cooperative Interactions between 480 kDa Ankyrin-G and EB Proteins Assemble the Axon Initial Segment. J Neurosci. 2016; 36(16):4421-33. PMC: 6601828. DOI: 10.1523/JNEUROSCI.3219-15.2016. View

13.

Maduro M, Pilgrim D . Identification and cloning of unc-119, a gene expressed in the Caenorhabditis elegans nervous system. Genetics. 1995; 141(3):977-88. PMC: 1206859. DOI: 10.1093/genetics/141.3.977. View

14.

Li S, Armstrong C, Bertin N, Ge H, Milstein S, Boxem M . A map of the interactome network of the metazoan C. elegans. Science. 2004; 303(5657):540-3. PMC: 1698949. DOI: 10.1126/science.1091403. View

15.

Bennett V, Lorenzo D . An Adaptable Spectrin/Ankyrin-Based Mechanism for Long-Range Organization of Plasma Membranes in Vertebrate Tissues. Curr Top Membr. 2016; 77:143-84. DOI: 10.1016/bs.ctm.2015.10.001. View

16.

Jegla T, Nguyen M, Feng C, Goetschius D, Luna E, van Rossum D . Bilaterian Giant Ankyrins Have a Common Evolutionary Origin and Play a Conserved Role in Patterning the Axon Initial Segment. PLoS Genet. 2016; 12(12):e1006457. PMC: 5135030. DOI: 10.1371/journal.pgen.1006457. View

17.

Tsuboi D, Hikita T, Qadota H, Amano M, Kaibuchi K . Regulatory machinery of UNC-33 Ce-CRMP localization in neurites during neuronal development in Caenorhabditis elegans. J Neurochem. 2005; 95(6):1629-41. DOI: 10.1111/j.1471-4159.2005.03490.x. View

18.

Baas P, Black M, Banker G . Changes in microtubule polarity orientation during the development of hippocampal neurons in culture. J Cell Biol. 1989; 109(6 Pt 1):3085-94. PMC: 2115969. DOI: 10.1083/jcb.109.6.3085. View

19.

Lu W, Fox P, Lakonishok M, Davidson M, Gelfand V . Initial neurite outgrowth in Drosophila neurons is driven by kinesin-powered microtubule sliding. Curr Biol. 2013; 23(11):1018-23. PMC: 3676710. DOI: 10.1016/j.cub.2013.04.050. View

20.

Dickinson D, Pani A, Heppert J, Higgins C, Goldstein B . Streamlined Genome Engineering with a Self-Excising Drug Selection Cassette. Genetics. 2015; 200(4):1035-49. PMC: 4574250. DOI: 10.1534/genetics.115.178335. View