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An activity-modulated transport route across myelin (TRAM) for motor-driven organelle transfer in oligodendrocytes
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DOI：10.1038/s41593-026-02383-0.png)
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Abstract
En 中文
Myelin sheaths comprise compacted layers of membrane wrapped around axons. Each sheath, if ‘unwrapped’, has a cytoplasm-filled space at its perimeter. Transmission electron microscopy reveals that this space contains microtubules and organelles; however, whether these are developmental remnants or serve a specific function remains unknown. Live imaging of myelinating oligodendrocytes in mice showed microtubule-dependent organelle transport within myelin sheath cytoplasmic spaces. Further, movement of myelin-located peroxisomes was modulated by neuronal electrical activity, in vitro and in vivo. Loss of oligodendroglial KIF21B and/or CNP in vivo led to the apparent stasis of myelin organelles and secondary axon pathology. We, thus, propose the acronym TRAM (transport route across myelin), defining the continuous cytoplasmic network in oligodendrocytes and myelin. This system, comprising the inner and outer tongues and paranodal loops, spans compact myelin and enables transport of metabolites and organelles between the oligodendrocyte soma and the periaxonal space. Axons require intracellular transport of cargoes between the soma and the terminus. The authors show a related logistical challenge exists at smaller scale with respect to the interaction of process-bearing oligodendrocytes and the axons they myelinate.
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