A Golgi-associated lipid kinase controls peripheral nerve myelination.

Myelination of axons in the central nervous system and peripheral nervous system (PNS) of vertebrates including humans enables the fast, saltatory propagation of nerve impulses by restricting action potentials to short unmyelinated axonal segments termed nodes of Ranvier (1). Defects in nerve myelination are causative of a variety of myelin diseases that range from leukodystrophies to peripheral neuropathies with demyelination such as the genetically heterogenous group of Charcot-Marie Tooth (CMT) (2) disease or nonhereditary neuropathies caused by diabetes and infections. Despite the fact that the formation of myelin provides a unique secretory challenge to myelin-producing cells, we know surprisingly little about the underlying cell biological processes. In PNAS, Baba et al. (3) identify a crucial role for the Golgi-associated phosphatidylinositol 4-kinase type IIIβ (PI4KB) in the myelination of peripheral nerves by Schwann cells.\n\nMyelin in the PNS forms as a spiral extension of the Schwann cell plasma membrane, which wraps around its target axon by lateral and radial expansion followed by compaction into the characteristic periodic layering of the myelin sheath (1). In the PNS, only axons with a diameter of 1 μm or more are myelinated, while small-diameter axons, in particular group C nerve fibers, are unmyelinated and grouped together in so-called Remak bundles. Myelinated compact axonal segments (internodes) are interspersed by nodes of Ranvier, where axonal sodium channels are concentrated (1). Previous studies have uncovered crucial cell-autonomous functions for lipids and lipid-metabolizing enzymes including phosphatidylinositol (PI) kinases and phosphatases in the regulation of myelin biogenesis (2, 4, 5).\n\nHence, Baba et al. (3) generated conditional knockout (cKO) mice specifically lacking PI4KB, an enzyme thought to contribute the majority of phosphatidylinositol 4-phosphate [PI(4)P]-synthesizing activity to the Golgi complex (6), in peripheral myelin-producing Schwann cells. The Golgi complex functions as a major sorting station for protein secretion … \n\n[↵][1]1To whom correspondence may be addressed. Email: haucke{at}fmp-berlin.de.\n\n [1]: #xref-corresp-1-1