Oligodendrocytes express synaptic proteins that modulate myelin sheath formation

Bruce Appel,Alexandria N Hughes

doi:10.1038/s41467-019-12059-y

Bruce Appel, Alexandria N Hughes

Open Access

https://doi.org/10.1038/s41467-019-12059-y

Copy DOI

Abstract

Vesicular release from neurons promotes myelin sheath growth on axons. Oligodendrocytes express proteins that allow dendrites to respond to vesicular release at synapses, suggesting that axon-myelin contacts use similar communication mechanisms as synapses to form myelin sheaths. To test this, we used fusion proteins to track synaptic vesicle localization and membrane fusion in zebrafish during developmental myelination and investigated expression and localization of PSD95, a dendritic post-synaptic protein, within oligodendrocytes. Synaptic vesicles accumulate and exocytose at ensheathment sites with variable patterning and most sheaths localize PSD95 with patterning similar to exocytosis site location. Disruption of candidate PDZ-binding transsynaptic adhesion proteins in oligodendrocytes cause variable effects on sheath length and number. One candidate, Cadm1b, localizes to myelin sheaths where both PDZ binding and extracellular adhesion to axons mediate sheath growth. Our work raises the possibility that axon-glial communication contributes to myelin plasticity, providing new targets for mechanistic unraveling of developmental myelination.

Highlights

Vesicular release from neurons promotes myelin sheath growth on axons
We focused on one candidate, Cadm1b (SynCAM1), and found that it localizes to myelin sheaths, where its PDZ binding motif is required for myelin sheath growth
We investigated oligodendrocyte expression and localization of the membrane-associated guanylate kinase (MAGUK) postsynaptic density protein 95 (PSD95), a scaffold known for anchoring neurotransmitter receptors at excitatory postsynaptic terminals, to learn if myelin sheaths have

Summary

Introduction

Vesicular release from neurons promotes myelin sheath growth on axons. Oligodendrocytes express proteins that allow dendrites to respond to vesicular release at synapses, suggesting that axon-myelin contacts use similar communication mechanisms as synapses to form myelin sheaths. Oligodendrocytes express numerous genes encoding neurotransmitter receptors, synaptic scaffolds, transsynaptic adhesion molecules, and Rho-GTPases[14,15,16] that, when expressed by neurons, endow dendrites with the ability to detect and respond to release at synapses. Similar to their function in dendrites, these proteins may allow oligodendrocytes to sense, adhere, and respond to axonal secretion[17]. To test whether the synaptic features of the axonmyelin interface are important for normal myelination, we manipulated synaptogenic adhesion proteins in oligodendrocytes When these same proteins are disrupted in neurons, synaptogenesis falters and synapses are abnormal in size and number. Our work suggests shared mechanisms of synaptic and myelin plasticity and raises the possibility that synaptogenic factors have previously unrecognized roles in developmental myelination

Methods

Results

Conclusion