ArticleProceedings of the National Academy of Sciences of the United States of America2020
Myelination of peripheral nerves is controlled by PI4KB through regulation of Schwann cell Golgi function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 25 citations in OpenAlex.
- The mechanistic basis of cargo selection during Golgi maturation.Science advances · 2025Article
- Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- Molecular and cellular mechanisms underlying peripheral nerve injury-induced cellular ecological shifts: Implications for neuroregeneration.IBRO neuroscience reports · 2025Review
- Phosphoinositide Metabolism: Biochemistry, Physiology and Genetic Disorders.Journal of inherited metabolic disease · 2025Review
- Schwann Cell-Specific Ablation of Beclin 1 Impairs Myelination and Leads to Motor and Sensory Neuropathy in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ARMH3 is an ARL5 effector that promotes PI4KB-catalyzed PI4P synthesis at the trans-Golgi network.Nature communications · 2024Article
- PI4KIIIβ-Mediated Phosphoinositides Metabolism Regulates Function of the VTA Dopaminergic Neurons and Depression-Like Behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- PI(4,5)P2-dependent and -independent roles of PI4P in the control of hormone secretion by pituitary cells.Frontiers in endocrinology · 2023Review
- Phosphoinositides as membrane organizers.Nature reviews. Molecular cell biology · 2022Review
- PI4K2A deficiency causes innate error in intracellular trafficking with developmental and epileptic-dyskinetic encephalopathy.Annals of clinical and translational neurology · 2022Article
- Biallelic PI4KA variants cause neurological, intestinal and immunological disease.Brain : a journal of neurology · 2021Article
- Myelin Biology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Control of Neuronal Excitability by Cell Surface Receptor Density and Phosphoinositide Metabolism.Frontiers in pharmacology · 2021Article
- Phosphoinositides: Roles in the Development of Microglial-Mediated Neuroinflammation and Neurodegeneration.Frontiers in cellular neuroscience · 2021Review
- A Golgi-associated lipid kinase controls peripheral nerve myelination.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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