PIKE is essential for oligodendroglia development and CNS myelination

Chi Bun Chan; Xia Liu; Lixia Zhao; Guanglu Liu; Chi Wai Lee; Yue Feng; Keiqang Ye

doi:10.1073/pnas.1318185111

PIKE is essential for oligodendroglia development and CNS myelination

Chi Bun Chan
, Xia Liu
, Lixia Zhao
, Guanglu Liu
, Chi Wai Lee
, Yue Feng^*
, Keiqang Ye^*

^*Corresponding author for this work

Department of Biology

Research output: Contribution to journal › Journal article › peer-review

16 Citations (Scopus)

Abstract

Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide- 3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE^-/-) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE^-/- OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE^-/- mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE^-/- brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.

Original language	English
Pages (from-to)	1993-1998
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	111
Issue number	5
Early online date	21 Jan 2014
DOIs	https://doi.org/10.1073/pnas.1318185111
Publication status	Published - 4 Feb 2014

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@article{253a2ee43aa54d16a9fcbfcffc809762,

title = "PIKE is essential for oligodendroglia development and CNS myelination",

abstract = "Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide- 3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE-/-) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE-/- OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE-/- mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE-/- brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.",

author = "Chan, \{Chi Bun\} and Xia Liu and Lixia Zhao and Guanglu Liu and Lee, \{Chi Wai\} and Yue Feng and Keiqang Ye",

note = "Funding Information: The authors thank Reed Otten for reading the manuscript. This work is supported by National Institutes of Health Grant R01NS045627 (to K.Y.) and Grant R01NS056097 (to Y.F.). Publisher copyright: Chan et al.",

year = "2014",

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doi = "10.1073/pnas.1318185111",

language = "English",

volume = "111",

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journal = "Proceedings of the National Academy of Sciences of the United States of America",

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TY - JOUR

T1 - PIKE is essential for oligodendroglia development and CNS myelination

AU - Chan, Chi Bun

AU - Liu, Xia

AU - Zhao, Lixia

AU - Liu, Guanglu

AU - Lee, Chi Wai

AU - Feng, Yue

AU - Ye, Keiqang

N1 - Funding Information: The authors thank Reed Otten for reading the manuscript. This work is supported by National Institutes of Health Grant R01NS045627 (to K.Y.) and Grant R01NS056097 (to Y.F.). Publisher copyright: Chan et al.

PY - 2014/2/4

Y1 - 2014/2/4

N2 - Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide- 3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE-/-) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE-/- OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE-/- mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE-/- brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.

AB - Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide- 3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE-/-) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE-/- OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE-/- mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE-/- brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.

UR - https://www.scopus.com/pages/publications/84893463527

U2 - 10.1073/pnas.1318185111

DO - 10.1073/pnas.1318185111

M3 - Journal article

C2 - 24449917

SN - 0027-8424

VL - 111

SP - 1993

EP - 1998

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 5

ER -

PIKE is essential for oligodendroglia development and CNS myelination

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