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bioRxiv · 10.1101/2024.06.02.591488

A myelinic channel system for organelle transport to the glial-axonal junction

Edgar, J. M.·Chapple, K. J.·Wirth, S.·Chen, Y.-H.·Gerwig, U.·Aicher, M. L.·Kim, Y.·Green, T.·Komarek, L.·Brown, A. M.·Pardo-Fernandez, L.·Crawford, C. L.·Smith, R. S.·Werner, H. B.·Kassmann, C.·Kneussel, M.·Brown, E. R.·Goebbels, S.·Nave, K.-A.
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Abstract

Myelin sheaths comprise compacted layers of oligodendroglial membrane wrapped spirally around axons. Each sheath, if imagined unwrapped, has a cytoplasm-filled space at its perimeter, linking it to the oligodendrocyte soma via a short process. By electron microscopy (EM), this space, which we term the myelinic channel system contains microtubules and membranous organelles, but whether these are remnants of development or serve a function is unknown. Performing live imaging of myelinating oligodendrocytes expressing fluorescent reporters, we found that the myelinic channel system serves microtubule-dependent organelle transport. Further, the intra-myelinic movement of peroxisomes was modulated by neuronal electrical activity in these mixed neural cell cultures. Loss of oligodendroglial Kif21b or CNP in vivo led to apparent stasis of myelin organelles and secondary axon pathology. This suggests that oligodendrocytes require motor transport in myelin to maintain axonal integrity.

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Edgar, J. M., Chapple, K. J., Wirth, S., Chen, Y.-H., Gerwig, U., Aicher, M. L., Kim, Y., Green, T., Komarek, L., Brown, A. M., Pardo-Fernandez, L., Crawford, C. L., Smith, R. S., Werner, H. B., Kassmann, C., Kneussel, M., Brown, E. R., Goebbels, S., Nave, K.-A.. 2024-06-03. A myelinic channel system for organelle transport to the glial-axonal junction. https://doi.org/10.1101/2024.06.02.591488

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