This research investigates how oligodendrocytes sense and respond to the physical dimensions of the axons they wrap in myelin. The study identifies TMEM63A as a critical mechanosensitive ion channel that allows these cells to convert mechanical pressure into calcium signaling during development. Through experiments with knockout mice and zebrafish, the authors demonstrate that a lack of this channel leads to shorter myelin segments, wider gaps between nodes, and slower nerve conduction. These biological defects manifest as gait and motor coordination issues in animal models, mirroring symptoms found in human patients with specific leukodystrophies. Furthermore, the findings suggest that TMEM63A regulates the transport of essential myelin proteins like MBP via the motor protein MYO5A. Ultimately, the sources highlight a specialized form of cell-cell communication where glia use mechanical cues to ensure the structural integrity of neural circuits.

References:

• Dereddi R R, Djannatian M, Fiore F, et al. Oligodendrocyte mechanotransduction channel TMEM63A regulates myelin sheath geometry[J]. Neuron, 2026.