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 Caenorhabditis elegans, 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.
| Original language | English |
|---|---|
| Article number | e55111 |
| Number of pages | 32 |
| Journal | eLife |
| Volume | 9 |
| DOIs | |
| Publication status | Published - 1 Apr 2020 |
Funding
We thanks Mike Boxem and Sander van den Heuvel (Utrecht University, The Netherlands) for advice, C. elegans reagents and infrastructure, Yujie Cao for technical assistance with the pull-down experiments, Thijs Koorman, Dipti Rai and Anna Akhmanova for experiments related to this study that were not included, G Ou for sharing unpublished results and Lukas Kapitein, Mithila Burute and Amelie Fréal for discussions and critically reading the manuscript. We acknowledge Gert Jansen, Cori Bargmann, Kang Shen and Kunihiro Matsumo for kind sharing of C. elegans strains and reagents. Some strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440) and some by the National Biorescource Project. We thank WormBase for curating and making available data related to C. elegans. This work was funded by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) (NWO-ALW-VENI 863.12.001 to MH, NWO-ALW-VICI 865.10.010 to CCH), by the European Research Council (ERC Consolidator Grant 617050 to CCH, ERC starting grant 715243 to MK), HFSP-CDA (CDA00023/2018) to MK, European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 754510 (PROBIST) and by the Chinese Scholarship Council scholarship (CSC) to LH. MK acknowledges financial support from the Spanish Ministry of Economy and Competitiveness (SEV-2015–0522, RYC-2015–17935), from Funda-ció Privada Cellex, and from Generalitat de Catalunya through the CERCA program and (AGAUR) 2017 SGR 1012.