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@ARTICLE{Dereddi:285352,
author = {Dereddi, Ram R and Djannatian, Minou and Fiore, Frederic
and Kalita, Darshana and Verkest, Clement and Torres, Felipe
Bodaleo and Möbius, Wiebke and Khodaie, Babak and Ruhwedel,
Torben and Alhalaseh, Khaleel and Schifferer, Martina and
Wirth, Angela and Hill, Anthony and Ottenheijm, Roger and
Patrizi, Annarita and Kann, Oliver and Lechner, Stefan G and
Freichel, Marc and Agarwal, Amit},
title = {{O}ligodendrocyte mechanotransduction channel {TMEM}63{A}
regulates myelin sheath geometry.},
journal = {Neuron},
volume = {114},
number = {4},
issn = {0896-6273},
address = {[Cambridge, Mass.]},
publisher = {Cell Press},
reportid = {DZNE-2026-00218},
pages = {699 - 723.e11},
year = {2026},
abstract = {Oligodendrocytes, the myelinating cells of the central
nervous system, precisely sculpt their insulating membranes
to match axon size, ensuring fine-tuned action potential
propagation. How oligodendrocytes estimate axon caliber to
adapt myelin sheath geometry is unknown. The biochemical
measure of axonal size provided by neuregulin 1 for Schwann
cells is dispensable in oligodendrocytes, and we reasoned
that biophysical cues might instead be required. By
combining transcriptomics, in vivo optical imaging, and
electron microscopy in mouse and zebrafish models, we
identified TMEM63A as a key mechanosensitive channel in
oligodendrocytes. TMEM63A enabled oligodendrocytes to sense
membrane stretch and translate it into Ca2+ signals. In the
absence of TMEM63A, developmental myelination was severely
impaired with shorter and thinner myelin sheaths on
large-diameter axons, ectopic myelination of very
small-diameter axons, and increased sheath retractions. We
propose MYO5A-dependent Mbp mRNA targeting to the nascent
myelin sheaths as a mechanism linking stretch-activated Ca2+
signaling to myelin formation and sheath geometry
refinement.},
keywords = {Animals / Myelin Sheath: metabolism / Myelin Sheath:
ultrastructure / Zebrafish / Mice / Mechanotransduction,
Cellular: physiology / Oligodendroglia: metabolism /
Oligodendroglia: ultrastructure / Axons: metabolism /
Zebrafish Proteins: genetics / Zebrafish Proteins:
metabolism / Calcium Signaling: physiology / Myelin Basic
Protein: metabolism / Myelin Basic Protein: genetics / HLD19
(Other) / MBP transport (Other) / TMEM63A (Other) /
axon-glia interactions (Other) / calcium signaling (Other) /
mechanical forces (Other) / mechanotransduction channels
(Other) / myelination (Other) / myosin5a (Other) /
oligodendrocyte (Other) / transient infantile
hypomyelinating leukodystrophy-19 (Other) / Zebrafish
Proteins (NLM Chemicals) / Myelin Basic Protein (NLM
Chemicals)},
cin = {AG Simons / AG Misgeld},
ddc = {610},
cid = {I:(DE-2719)1110008 / I:(DE-2719)1110000-4},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41483808},
doi = {10.1016/j.neuron.2025.11.009},
url = {https://pub.dzne.de/record/285352},
}