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Neurons define non-myelinated axon segments by the regulation of galectin-4-containing axon membrane domains

Natalia Díez-Revuelta, Alonso M. Higuero, Silvia Velasco, María Peñas-de-la-Iglesia, Hans-Joachim Gabius, José Abad-Rodríguez
doi: https://doi.org/10.1101/115758
Natalia Díez-Revuelta
1Membrane Biology and Axonal Repair Laboratory. Hospital Nacional de Parapéjicos (SESCAM), Finca La Peraleda s/n, E-45071 Toledo, Spain
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Alonso M. Higuero
1Membrane Biology and Axonal Repair Laboratory. Hospital Nacional de Parapéjicos (SESCAM), Finca La Peraleda s/n, E-45071 Toledo, Spain
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Silvia Velasco
1Membrane Biology and Axonal Repair Laboratory. Hospital Nacional de Parapéjicos (SESCAM), Finca La Peraleda s/n, E-45071 Toledo, Spain
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María Peñas-de-la-Iglesia
1Membrane Biology and Axonal Repair Laboratory. Hospital Nacional de Parapéjicos (SESCAM), Finca La Peraleda s/n, E-45071 Toledo, Spain
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Hans-Joachim Gabius
2Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität, Veterinärstr. I3, D-80539 München,Germany
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José Abad-Rodríguez
1Membrane Biology and Axonal Repair Laboratory. Hospital Nacional de Parapéjicos (SESCAM), Finca La Peraleda s/n, E-45071 Toledo, Spain
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  • For correspondence: jabadr@jccm.sescam.es
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Abstract

The mechanism underlying selective myelination of axons versus dendrites or neuronal somata relies on the expression of somatodendritic membrane myelination inhibitors (i.e. JAM2). However, axons still present long unmyelinated segments proposed to contribute to axonal plasticity and higher order brain functions. Why these segments remain unmyelinated is still an unresolved issue. The bifunctional lectin galectin-4 (Gal-4) organizes the transport of axon glycoproteins by binding to N-acetyllactosamine (LacNac) termini of N-glycans. We have shown that Gal-4 is sorted to segmental domains (G4Ds) along the axon surface, reminiscent of these long unmyelinated axon segments in cortical neurons. We report here that oligodendrocytes (OLGs) do not deposit myelin on Gal-4 covered surfaces or myelinate axonal G4Ds. In addition, Gal-4 interacts and co-localizes in G4Ds with contactin-1, a marker of non-myelinated nodes of Ranvier. Neither Gal-4 expression nor G4D dimensions are affected by myelin extracts or myelinating OLGs, but are reduced with neuron maturation. As in vitro, Gal-4 is consistently segregated from myelinated structures in the brain. Our data shape the novel concept that neurons establish and regulate axon membrane domains expressing Gal-4, the first inhibitor of myelination identified in axons, whose boundaries delineate myelination-incompetent axon segments along neuron development.

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Posted March 10, 2017.
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Neurons define non-myelinated axon segments by the regulation of galectin-4-containing axon membrane domains
Natalia Díez-Revuelta, Alonso M. Higuero, Silvia Velasco, María Peñas-de-la-Iglesia, Hans-Joachim Gabius, José Abad-Rodríguez
bioRxiv 115758; doi: https://doi.org/10.1101/115758
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Neurons define non-myelinated axon segments by the regulation of galectin-4-containing axon membrane domains
Natalia Díez-Revuelta, Alonso M. Higuero, Silvia Velasco, María Peñas-de-la-Iglesia, Hans-Joachim Gabius, José Abad-Rodríguez
bioRxiv 115758; doi: https://doi.org/10.1101/115758

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