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Acsl, the Drosophila Ortholog of Intellectual-disability-related ACSL4, Inhibits Synaptic Growth by Altered Lipids
Yan Huang, Sheng Huang, Sin Man Lam, Zhihua Liu, Guanghou Shui and Yong Q. Zhang
Journal of Cell Science
Abstract
Nervous system development and function are tightly regulated by metabolic processes, including the metabolism of lipids such as fatty acids. Mutations in long-chain acyl-CoA synthetase 4 (ACSL4) are associated with non-syndromic intellectual disabilities. We previously reported that Acsl, the Drosophila ortholog of mammalian ACSL3 and ACSL4, inhibits neuromuscular synapse growth by suppressing bone morphogenetic protein (BMP) signaling. Here, we report that Acsl regulates the composition of fatty acids and membrane lipids, which in turn affects neuromuscular junction (NMJ) synapse development. Acsl mutant brains had a decreased abundance of C16:1 fatty acyls; restoration of Acsl expression abrogated NMJ overgrowth and the increase in BMP signaling. A lipidomic analysis revealed that Acsl suppressed the levels of three lipid raft components in the brain, includingmannosyl glucosylceramide (MacCer), phosphoethanolamine ceramide and ergosterol. TheMacCer levelwas elevated in Acsl mutant NMJs and, along with sterol, promoted NMJ overgrowth, but was not associated with the increase in BMP signaling in the mutants. These findings suggest that Acsl inhibits NMJ growth by stimulating C16:1 fatty acyl production and concomitantly suppressing raft-associated lipid levels.
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论文编号: |
DOI:10.1242/jcs.195032 |
论文题目: |
Acsl, the Drosophila Ortholog of Intellectual-disability-related ACSL4, Inhibits Synaptic Growth by Altered Lipids |
英文论文题目: |
Acsl, the Drosophila Ortholog of Intellectual-disability-related ACSL4, Inhibits Synaptic Growth by Altered Lipids |
第一作者: |
Yan Huang, Sheng Huang, Sin Man Lam, Zhihua Liu, Guanghou Shui and Yong Q. Zhang |
英文第一作者: |
Yan Huang, Sheng Huang, Sin Man Lam, Zhihua Liu, Guanghou Shui and Yong Q. Zhang |
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2016-11-26 |
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摘要: |
Nervous system development and function are tightly regulated by metabolic processes, including the metabolism of lipids such as fatty acids. Mutations in long-chain acyl-CoA synthetase 4 (ACSL4) are associated with non-syndromic intellectual disabilities. We previously reported that Acsl, the Drosophila ortholog of mammalian ACSL3 and ACSL4, inhibits neuromuscular synapse growth by suppressing bone morphogenetic protein (BMP) signaling. Here, we report that Acsl regulates the composition of fatty acids and membrane lipids, which in turn affects neuromuscular junction (NMJ) synapse development. Acsl mutant brains had a decreased abundance of C16:1 fatty acyls; restoration of Acsl expression abrogated NMJ overgrowth and the increase in BMP signaling. A lipidomic analysis revealed that Acsl suppressed the levels of three lipid raft components in the brain, includingmannosyl glucosylceramide (MacCer), phosphoethanolamine ceramide and ergosterol. TheMacCer levelwas elevated in Acsl mutant NMJs and, along with sterol, promoted NMJ overgrowth, but was not associated with the increase in BMP signaling in the mutants. These findings suggest that Acsl inhibits NMJ growth by stimulating C16:1 fatty acyl production and concomitantly suppressing raft-associated lipid levels. |
英文摘要: |
Nervous system development and function are tightly regulated by metabolic processes, including the metabolism of lipids such as fatty acids. Mutations in long-chain acyl-CoA synthetase 4 (ACSL4) are associated with non-syndromic intellectual disabilities. We previously reported that Acsl, the Drosophila ortholog of mammalian ACSL3 and ACSL4, inhibits neuromuscular synapse growth by suppressing bone morphogenetic protein (BMP) signaling. Here, we report that Acsl regulates the composition of fatty acids and membrane lipids, which in turn affects neuromuscular junction (NMJ) synapse development. Acsl mutant brains had a decreased abundance of C16:1 fatty acyls; restoration of Acsl expression abrogated NMJ overgrowth and the increase in BMP signaling. A lipidomic analysis revealed that Acsl suppressed the levels of three lipid raft components in the brain, includingmannosyl glucosylceramide (MacCer), phosphoethanolamine ceramide and ergosterol. TheMacCer levelwas elevated in Acsl mutant NMJs and, along with sterol, promoted NMJ overgrowth, but was not associated with the increase in BMP signaling in the mutants. These findings suggest that Acsl inhibits NMJ growth by stimulating C16:1 fatty acyl production and concomitantly suppressing raft-associated lipid levels. |
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Journal of Cell Science |
英文刊物名称: |
Journal of Cell Science |
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其它备注: |
Yan Huang, Sheng Huang, Sin Man Lam, Zhihua Liu, Guanghou Shui and Yong Q. Zhang. Acsl, the Drosophila Ortholog of Intellectual-disability-related ACSL4, Inhibits Synaptic Growth by Altered Lipids. Journal of Cell Science. DOI:10.1242/jcs.195032 |
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