Schwann Cell Myelination Requires Timely and Precise Targeting of P0 Protein
Open Access
- 6 March 2000
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 148 (5) , 1009-1020
- https://doi.org/10.1083/jcb.148.5.1009
Abstract
This report investigated mechanisms responsible for failed Schwann cell myelination in mice that overexpress P0 (P0tg), the major structural protein of PNS myelin. Quantitative ultrastructural immunocytochemistry established that P0 protein was mistargeted to abaxonal, periaxonal, and mesaxon membranes in P0tg Schwann cells with arrested myelination. The extracellular leaflets of P0-containing mesaxon membranes were closely apposed with periodicities of compact myelin. The myelin-associated glycoprotein was appropriately sorted in the Golgi apparatus and targeted to periaxonal membranes. In adult mice, occasional Schwann cells myelinated axons possibly with the aid of endocytic removal of mistargeted P0. These results indicate that P0 gene multiplication causes P0 mistargeting to mesaxon membranes, and through obligate P0 homophilic adhesion, renders these dynamic membranes inert and halts myelination.Keywords
This publication has 49 references indexed in Scilit:
- Protein Sorting by Directed Maturation of Golgi CompartmentsScience, 1999
- Overexpression of 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase in Transgenic Mice Alters Oligodendrocyte Development and Produces Aberrant MyelinationMolecular and Cellular Neuroscience, 1996
- Glial cell degeneration and hypomyelination caused by overexpression of myelin proteolipid protein geneNeuron, 1994
- Two autosomal dominant neuropathies result from reciprocal DNA duplication/deletion of a region on chromosome 17Human Molecular Genetics, 1994
- Plasma membrane protein sorting in polarized epithelial cells.The Journal of cell biology, 1992
- Distribution of P0 protein and the myelin-associated glycoprotein in peripheral nerves from Trembler miceJournal of Neurocytology, 1991
- Cellular and Subcellular Distribution of 2′,3′‐Cyclic Nucleotide 3′‐Phosphodiesterase and Its mRNA in the Rat Central Nervous SystemJournal of Neurochemistry, 1988
- Viral glycoproteins destined for apical or basolateral plasma membrane domains traverse the same Golgi apparatus during their intracellular transport in doubly infected Madin-Darby canine kidney cells.The Journal of cell biology, 1984
- Immunocytochemical localization of P0 protein in Golgi complex membranes and myelin of developing rat Schwann cells.The Journal of cell biology, 1981
- Studies on the control of myelinogenesis. II. Evidence for neuronal regulation of myelin productionBrain Research, 1976