001     285352
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024 7 _ |a 10.1016/j.neuron.2025.11.009
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024 7 _ |a 0896-6273
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024 7 _ |a 1097-4199
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037 _ _ |a DZNE-2026-00218
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Dereddi, Ram R
|b 0
245 _ _ |a Oligodendrocyte mechanotransduction channel TMEM63A regulates myelin sheath geometry.
260 _ _ |a [Cambridge, Mass.]
|c 2026
|b Cell Press
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
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650 _ 7 |a HLD19
|2 Other
650 _ 7 |a MBP transport
|2 Other
650 _ 7 |a TMEM63A
|2 Other
650 _ 7 |a axon-glia interactions
|2 Other
650 _ 7 |a calcium signaling
|2 Other
650 _ 7 |a mechanical forces
|2 Other
650 _ 7 |a mechanotransduction channels
|2 Other
650 _ 7 |a myelination
|2 Other
650 _ 7 |a myosin5a
|2 Other
650 _ 7 |a oligodendrocyte
|2 Other
650 _ 7 |a transient infantile hypomyelinating leukodystrophy-19
|2 Other
650 _ 7 |a Zebrafish Proteins
|2 NLM Chemicals
650 _ 7 |a Myelin Basic Protein
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Myelin Sheath: metabolism
|2 MeSH
650 _ 2 |a Myelin Sheath: ultrastructure
|2 MeSH
650 _ 2 |a Zebrafish
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mechanotransduction, Cellular: physiology
|2 MeSH
650 _ 2 |a Oligodendroglia: metabolism
|2 MeSH
650 _ 2 |a Oligodendroglia: ultrastructure
|2 MeSH
650 _ 2 |a Axons: metabolism
|2 MeSH
650 _ 2 |a Zebrafish Proteins: genetics
|2 MeSH
650 _ 2 |a Zebrafish Proteins: metabolism
|2 MeSH
650 _ 2 |a Calcium Signaling: physiology
|2 MeSH
650 _ 2 |a Myelin Basic Protein: metabolism
|2 MeSH
650 _ 2 |a Myelin Basic Protein: genetics
|2 MeSH
700 1 _ |a Djannatian, Minou
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700 1 _ |a Fiore, Frederic
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700 1 _ |a Kalita, Darshana
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700 1 _ |a Verkest, Clement
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700 1 _ |a Torres, Felipe Bodaleo
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700 1 _ |a Möbius, Wiebke
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700 1 _ |a Khodaie, Babak
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700 1 _ |a Ruhwedel, Torben
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700 1 _ |a Alhalaseh, Khaleel
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700 1 _ |a Schifferer, Martina
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700 1 _ |a Wirth, Angela
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700 1 _ |a Hill, Anthony
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700 1 _ |a Ottenheijm, Roger
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700 1 _ |a Patrizi, Annarita
|b 14
700 1 _ |a Kann, Oliver
|b 15
700 1 _ |a Lechner, Stefan G
|b 16
700 1 _ |a Freichel, Marc
|b 17
700 1 _ |a Agarwal, Amit
|b 18
773 _ _ |a 10.1016/j.neuron.2025.11.009
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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