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Intra- and intercellular trafficking in sphingolipid metabolism in myelination.

ABSTRACT: The myelin sheath, produced by oligodendrocytes in the central nervous system, provides essential electrical insulation to neurons, but also is critical for viability of neurons. Both the protein and lipid composition of this fascinating membrane is unique. Here the focus is on the sphingolipids that are highly abundant in myelin and, in particular, how they are produced. This review discusses how sphingolipid metabolism is regulated. In particular the subcellular localization of lipid metabolic enzymes is discussed and how inter-organelle transport can affect the metabolic routes that sphingolipid precursors take. Understanding the regulation of sphingolipid metabolism in formation of the myelin membrane will have a significant impact on strategies to treat demyelinating diseases.

SUBMITTER: Wattenberg BW

PROVIDER: S-EPMC6469711 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Intra- and intercellular trafficking in sphingolipid metabolism in myelination.

Wattenberg Binks W BW

Advances in biological regulation 20181123

The myelin sheath, produced by oligodendrocytes in the central nervous system, provides essential electrical insulation to neurons, but also is critical for viability of neurons. Both the protein and lipid composition of this fascinating membrane is unique. Here the focus is on the sphingolipids that are highly abundant in myelin and, in particular, how they are produced. This review discusses how sphingolipid metabolism is regulated. In particular the subcellular localization of lipid metabolic ...[more]

PMID: 30497846

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Project description:Local synthesis of proteins within the Schwann cell periphery is extremely important for efficient process extension and myelination, when cells undergo dramatic changes in polarity and geometry. Still, it is unclear how ribosomal distributions are developed and maintained within Schwann cell projections to sustain local translation. In this multi-disciplinary study, we expressed a plasmid encoding a fluorescently labeled ribosomal subunit (L4-GFP) in cultured primary rat Schwann cells. This enabled the generation of high-resolution, quantitative data on ribosomal distributions and trafficking dynamics within Schwann cells during early stages of myelination, induced by ascorbic acid treatment. Ribosomes were distributed throughout Schwann cell projections, with ~2-3 bright clusters along each projection. Clusters emerged within 1 day of culture and were maintained throughout early stages of myelination. Three days after induction of myelination, net ribosomal movement remained anterograde (directed away from the Schwann cell body), but ribosomal velocity decreased to about half the levels of the untreated group. Statistical and modeling analysis provided additional insight into key factors underlying ribosomal trafficking. Multiple regression analysis indicated that net transport at early time points was dependent on anterograde velocity, but shifted to dependence on anterograde duration at later time points. A simple, data-driven rate kinetics model suggested that the observed decrease in net ribosomal movement was primarily dictated by an increased conversion of anterograde particles to stationary particles, rather than changes in other directional parameters. These results reveal the strength of a combined experimental and theoretical approach in examining protein localization and transport, and provide evidence of an early establishment of ribosomal populations within Schwann cell projections with a reduction in trafficking following initiation of myelination.

Dataset Information

Intra- and intercellular trafficking in sphingolipid metabolism in myelination.

Publications

Intra- and intercellular trafficking in sphingolipid metabolism in myelination.

Similar Datasets

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