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000285352 1001_ $$aDereddi, Ram R$$b0
000285352 245__ $$aOligodendrocyte mechanotransduction channel TMEM63A regulates myelin sheath geometry.
000285352 260__ $$a[Cambridge, Mass.]$$bCell Press$$c2026
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000285352 520__ $$aOligodendrocytes, the myelinating cells of the central nervous system, precisely sculpt their insulating membranes to match axon size, ensuring fine-tuned action potential propagation. How oligodendrocytes estimate axon caliber to adapt myelin sheath geometry is unknown. The biochemical measure of axonal size provided by neuregulin 1 for Schwann cells is dispensable in oligodendrocytes, and we reasoned that biophysical cues might instead be required. By combining transcriptomics, in vivo optical imaging, and electron microscopy in mouse and zebrafish models, we identified TMEM63A as a key mechanosensitive channel in oligodendrocytes. TMEM63A enabled oligodendrocytes to sense membrane stretch and translate it into Ca2+ signals. In the absence of TMEM63A, developmental myelination was severely impaired with shorter and thinner myelin sheaths on large-diameter axons, ectopic myelination of very small-diameter axons, and increased sheath retractions. We propose MYO5A-dependent Mbp mRNA targeting to the nascent myelin sheaths as a mechanism linking stretch-activated Ca2+ signaling to myelin formation and sheath geometry refinement.
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000285352 650_7 $$2Other$$aHLD19
000285352 650_7 $$2Other$$aMBP transport
000285352 650_7 $$2Other$$aTMEM63A
000285352 650_7 $$2Other$$aaxon-glia interactions
000285352 650_7 $$2Other$$acalcium signaling
000285352 650_7 $$2Other$$amechanical forces
000285352 650_7 $$2Other$$amechanotransduction channels
000285352 650_7 $$2Other$$amyelination
000285352 650_7 $$2Other$$amyosin5a
000285352 650_7 $$2Other$$aoligodendrocyte
000285352 650_7 $$2Other$$atransient infantile hypomyelinating leukodystrophy-19
000285352 650_7 $$2NLM Chemicals$$aZebrafish Proteins
000285352 650_7 $$2NLM Chemicals$$aMyelin Basic Protein
000285352 650_2 $$2MeSH$$aAnimals
000285352 650_2 $$2MeSH$$aMyelin Sheath: metabolism
000285352 650_2 $$2MeSH$$aMyelin Sheath: ultrastructure
000285352 650_2 $$2MeSH$$aZebrafish
000285352 650_2 $$2MeSH$$aMice
000285352 650_2 $$2MeSH$$aMechanotransduction, Cellular: physiology
000285352 650_2 $$2MeSH$$aOligodendroglia: metabolism
000285352 650_2 $$2MeSH$$aOligodendroglia: ultrastructure
000285352 650_2 $$2MeSH$$aAxons: metabolism
000285352 650_2 $$2MeSH$$aZebrafish Proteins: genetics
000285352 650_2 $$2MeSH$$aZebrafish Proteins: metabolism
000285352 650_2 $$2MeSH$$aCalcium Signaling: physiology
000285352 650_2 $$2MeSH$$aMyelin Basic Protein: metabolism
000285352 650_2 $$2MeSH$$aMyelin Basic Protein: genetics
000285352 7001_ $$0P:(DE-2719)9000927$$aDjannatian, Minou$$b1$$udzne
000285352 7001_ $$aFiore, Frederic$$b2
000285352 7001_ $$aKalita, Darshana$$b3
000285352 7001_ $$aVerkest, Clement$$b4
000285352 7001_ $$aTorres, Felipe Bodaleo$$b5
000285352 7001_ $$aMöbius, Wiebke$$b6
000285352 7001_ $$aKhodaie, Babak$$b7
000285352 7001_ $$aRuhwedel, Torben$$b8
000285352 7001_ $$aAlhalaseh, Khaleel$$b9
000285352 7001_ $$0P:(DE-2719)2812260$$aSchifferer, Martina$$b10$$udzne
000285352 7001_ $$aWirth, Angela$$b11
000285352 7001_ $$aHill, Anthony$$b12
000285352 7001_ $$aOttenheijm, Roger$$b13
000285352 7001_ $$aPatrizi, Annarita$$b14
000285352 7001_ $$aKann, Oliver$$b15
000285352 7001_ $$aLechner, Stefan G$$b16
000285352 7001_ $$aFreichel, Marc$$b17
000285352 7001_ $$aAgarwal, Amit$$b18
000285352 773__ $$0PERI:(DE-600)2001944-0$$a10.1016/j.neuron.2025.11.009$$gVol. 114, no. 4, p. 699 - 723.e11$$n4$$p699 - 723.e11$$tNeuron$$v114$$x0896-6273$$y2026
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