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PI(3,5)P(2) biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms

Proper development of the CNS axon-glia unit requires bi-directional communication between axons and oligodendrocytes (OLs). We show that the signaling lipid phosphatidylinositol-3,5-bisphosphate [PI(3,5)P(2)] is required in neurons and in OLs for normal CNS myelination. In mice, mutations of Fig4,...

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Autores principales: Mironova, Yevgeniya A, Lenk, Guy M, Lin, Jing-Ping, Lee, Seung Joon, Twiss, Jeffery L, Vaccari, Ilaria, Bolino, Alessandra, Havton, Leif A, Min, Sang H, Abrams, Charles S, Shrager, Peter, Meisler, Miriam H, Giger, Roman J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889328/
https://www.ncbi.nlm.nih.gov/pubmed/27008179
http://dx.doi.org/10.7554/eLife.13023
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author Mironova, Yevgeniya A
Lenk, Guy M
Lin, Jing-Ping
Lee, Seung Joon
Twiss, Jeffery L
Vaccari, Ilaria
Bolino, Alessandra
Havton, Leif A
Min, Sang H
Abrams, Charles S
Shrager, Peter
Meisler, Miriam H
Giger, Roman J
author_facet Mironova, Yevgeniya A
Lenk, Guy M
Lin, Jing-Ping
Lee, Seung Joon
Twiss, Jeffery L
Vaccari, Ilaria
Bolino, Alessandra
Havton, Leif A
Min, Sang H
Abrams, Charles S
Shrager, Peter
Meisler, Miriam H
Giger, Roman J
author_sort Mironova, Yevgeniya A
collection PubMed
description Proper development of the CNS axon-glia unit requires bi-directional communication between axons and oligodendrocytes (OLs). We show that the signaling lipid phosphatidylinositol-3,5-bisphosphate [PI(3,5)P(2)] is required in neurons and in OLs for normal CNS myelination. In mice, mutations of Fig4, Pikfyve or Vac14, encoding key components of the PI(3,5)P(2) biosynthetic complex, each lead to impaired OL maturation, severe CNS hypomyelination and delayed propagation of compound action potentials. Primary OLs deficient in Fig4 accumulate large LAMP1(+) and Rab7(+) vesicular structures and exhibit reduced membrane sheet expansion. PI(3,5)P(2) deficiency leads to accumulation of myelin-associated glycoprotein (MAG) in LAMP1(+)perinuclear vesicles that fail to migrate to the nascent myelin sheet. Live-cell imaging of OLs after genetic or pharmacological inhibition of PI(3,5)P(2) synthesis revealed impaired trafficking of plasma membrane-derived MAG through the endolysosomal system in primary cells and brain tissue. Collectively, our studies identify PI(3,5)P(2) as a key regulator of myelin membrane trafficking and myelinogenesis. DOI: http://dx.doi.org/10.7554/eLife.13023.001
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spelling pubmed-48893282016-06-02 PI(3,5)P(2) biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms Mironova, Yevgeniya A Lenk, Guy M Lin, Jing-Ping Lee, Seung Joon Twiss, Jeffery L Vaccari, Ilaria Bolino, Alessandra Havton, Leif A Min, Sang H Abrams, Charles S Shrager, Peter Meisler, Miriam H Giger, Roman J eLife Neuroscience Proper development of the CNS axon-glia unit requires bi-directional communication between axons and oligodendrocytes (OLs). We show that the signaling lipid phosphatidylinositol-3,5-bisphosphate [PI(3,5)P(2)] is required in neurons and in OLs for normal CNS myelination. In mice, mutations of Fig4, Pikfyve or Vac14, encoding key components of the PI(3,5)P(2) biosynthetic complex, each lead to impaired OL maturation, severe CNS hypomyelination and delayed propagation of compound action potentials. Primary OLs deficient in Fig4 accumulate large LAMP1(+) and Rab7(+) vesicular structures and exhibit reduced membrane sheet expansion. PI(3,5)P(2) deficiency leads to accumulation of myelin-associated glycoprotein (MAG) in LAMP1(+)perinuclear vesicles that fail to migrate to the nascent myelin sheet. Live-cell imaging of OLs after genetic or pharmacological inhibition of PI(3,5)P(2) synthesis revealed impaired trafficking of plasma membrane-derived MAG through the endolysosomal system in primary cells and brain tissue. Collectively, our studies identify PI(3,5)P(2) as a key regulator of myelin membrane trafficking and myelinogenesis. DOI: http://dx.doi.org/10.7554/eLife.13023.001 eLife Sciences Publications, Ltd 2016-03-23 /pmc/articles/PMC4889328/ /pubmed/27008179 http://dx.doi.org/10.7554/eLife.13023 Text en © 2016, Mironova et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Mironova, Yevgeniya A
Lenk, Guy M
Lin, Jing-Ping
Lee, Seung Joon
Twiss, Jeffery L
Vaccari, Ilaria
Bolino, Alessandra
Havton, Leif A
Min, Sang H
Abrams, Charles S
Shrager, Peter
Meisler, Miriam H
Giger, Roman J
PI(3,5)P(2) biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms
title PI(3,5)P(2) biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms
title_full PI(3,5)P(2) biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms
title_fullStr PI(3,5)P(2) biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms
title_full_unstemmed PI(3,5)P(2) biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms
title_short PI(3,5)P(2) biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms
title_sort pi(3,5)p(2) biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889328/
https://www.ncbi.nlm.nih.gov/pubmed/27008179
http://dx.doi.org/10.7554/eLife.13023
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