A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning.
Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-09-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC3775723?pdf=render |
| _version_ | 1819155598180089856 |
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| author | Jack Jing Lin Wong Song Li Edwin Kok Hao Lim Yan Wang Cheng Wang Heng Zhang Daniel Kirilly Chunlai Wu Yih-Cherng Liou Hongyan Wang Fengwei Yu |
| author_facet | Jack Jing Lin Wong Song Li Edwin Kok Hao Lim Yan Wang Cheng Wang Heng Zhang Daniel Kirilly Chunlai Wu Yih-Cherng Liou Hongyan Wang Fengwei Yu |
| author_sort | Jack Jing Lin Wong |
| collection | DOAJ |
| description | Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. However, it is unknown which E3 ligase directs these two modes of pruning. Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body γ axons. The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb and promotes ddaC dendrite pruning downstream of EcR-B1 and Sox14, but independently of Mical. Moreover, we demonstrate that the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway. We show that the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination. Activation of the InR/PI3K/TOR pathway is sufficient to inhibit ddaC dendrite pruning. Thus, our findings provide a novel link between the E3 ligase and the InR/PI3K/TOR pathway during dendrite pruning. |
| first_indexed | 2024-12-22T15:39:31Z |
| format | Article |
| id | doaj.art-cf8118345f70406482d4679420718748 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-22T15:39:31Z |
| publishDate | 2013-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-cf8118345f70406482d46794207187482022-12-21T18:21:11ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852013-09-01119e100165710.1371/journal.pbio.1001657A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning.Jack Jing Lin WongSong LiEdwin Kok Hao LimYan WangCheng WangHeng ZhangDaniel KirillyChunlai WuYih-Cherng LiouHongyan WangFengwei YuPruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. However, it is unknown which E3 ligase directs these two modes of pruning. Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body γ axons. The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb and promotes ddaC dendrite pruning downstream of EcR-B1 and Sox14, but independently of Mical. Moreover, we demonstrate that the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway. We show that the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination. Activation of the InR/PI3K/TOR pathway is sufficient to inhibit ddaC dendrite pruning. Thus, our findings provide a novel link between the E3 ligase and the InR/PI3K/TOR pathway during dendrite pruning.http://europepmc.org/articles/PMC3775723?pdf=render |
| spellingShingle | Jack Jing Lin Wong Song Li Edwin Kok Hao Lim Yan Wang Cheng Wang Heng Zhang Daniel Kirilly Chunlai Wu Yih-Cherng Liou Hongyan Wang Fengwei Yu A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning. PLoS Biology |
| title | A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning. |
| title_full | A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning. |
| title_fullStr | A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning. |
| title_full_unstemmed | A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning. |
| title_short | A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning. |
| title_sort | cullin1 based scf e3 ubiquitin ligase targets the inr pi3k tor pathway to regulate neuronal pruning |
| url | http://europepmc.org/articles/PMC3775723?pdf=render |
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