Myelination of peripheral nerves is controlled by PI4KB through regulation of Schwann cell Golgi function
| Autor: | Takashi Baba, Zane N. Aldworth, Steve Wilson, Alejandro Alvarez-Prats, John E. Heuser, Tamas Balla, Mark Stopfer, Yeun Ju Kim, Daniel Abebe |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Schwann cell Golgi Apparatus Phosphatidylinositols Nerve conduction velocity Minor Histocompatibility Antigens 03 medical and health sciences Myelin symbols.namesake Mice 0302 clinical medicine Caveolae Commentaries medicine Animals Peripheral Nerves OSBP Myelin Sheath Mice Knockout Multidisciplinary Chemistry Golgi apparatus Cell biology Phosphotransferases (Alcohol Group Acceptor) 030104 developmental biology medicine.anatomical_structure Cholesterol nervous system symbols Schwann Cells Sphingomyelin 030217 neurology & neurosurgery PI4KB |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 |
| Popis: | Better understanding myelination of peripheral nerves would benefit patients affected by peripheral neuropathies, including Charcot-Marie-Tooth disease. Little is known about the role the Golgi compartment plays in Schwann cell (SC) functions. Here, we studied the role of Golgi in myelination of peripheral nerves in mice through SC-specific genetic inactivation of phosphatidylinositol 4-kinase beta (PI4KB), a Golgi-associated lipid kinase. Sciatic nerves of such mice showed thinner myelin of large diameter axons and gross aberrations in myelin organization affecting the nodes of Ranvier, the Schmidt-Lanterman incisures, and Cajal bands. Nonmyelinating SCs showed a striking inability to engulf small diameter nerve fibers. SCs of mutant mice showed a distorted Golgi morphology and disappearance of OSBP at the cis-Golgi compartment, together with a complete loss of GOLPH3 from the entire Golgi. Accordingly, the cholesterol and sphingomyelin contents of sciatic nerves were greatly reduced and so was the number of caveolae observed in SCs. Although the conduction velocity of sciatic nerves of mutant mice showed an 80% decrease, the mice displayed only subtle impairment in their motor functions. Our analysis revealed that Golgi functions supported by PI4KB are critically important for proper myelination through control of lipid metabolism, protein glycosylation, and organization of microvilli in the nodes of Ranvier of peripheral nerves. |
| Databáze: | OpenAIRE |
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