USP5/Leon deubiquitinase confines postsynaptic growth by maintaining ubiquitin homeostasis through Ubiquilin.
Synapse formation and growth are tightly controlled processes. How synaptic growth is terminated after reaching proper size remains unclear. Here, we show that Leon, the Drosophila USP5 deubiquitinase, controls postsynaptic growth. In leon mutants, postsynaptic specializations of neuromuscular junctions are dramatically expanded, including the subsynaptic reticulum, the postsynaptic density, and the glutamate receptor cluster. Expansion of these postsynaptic features is caused by a disruption of ubiquitin homeostasis with accumulation of free ubiquitin chains and ubiquitinated substrates in the leon mutant. Accumulation of Ubiquilin (Ubqn), the ubiquitin receptor whose human homolog ubiquilin 2 is associated with familial amyotrophic lateral sclerosis, also contributes to defects in postsynaptic growth and ubiquitin homeostasis. Importantly, accumulations of postsynaptic proteins cause different aspects of postsynaptic overgrowth in leon mutants. Thus, the deubiquitinase Leon maintains ubiquitin homeostasis and proper Ubqn levels, preventing postsynaptic proteins from accumulation to confine postsynaptic growth.
Pubmed ID: 28489002 RIS Download
Research resources used in this publication
- w[*]; P{w[+mW.hs]=GawB}D42 (RRID:BDSC_8816) (organism)
- w[1118]; P{GD4689}v41136/TM3 (RRID:FlyBase_FBst0463952) (organism)
- w[1118]; P{GD6741}v17567 (RRID:FlyBase_FBst0452773) (organism)
- w[1118]; P{GD4245}v30497 (RRID:FlyBase_FBst0458517) (organism)
- w[1118]; P{GD11310}v40512 (RRID:FlyBase_FBst0463603) (organism)
- y[1] w[*]; P{w[+mC]=UAS-mCD8::GFP.L}LL5, P{UAS-mCD8::GFP.L}2 (RRID:BDSC_5137) (organism)
- Schneider 2 (RRID:CVCL_Z232) (cell line)
- Pak[6]/TM3, Sb[1] Ser[1] (RRID:BDSC_8809) (organism)
- w[*]; P{w[+mW.hs]=GAL4-da.G32}UH1, Sb[1]/TM6B, Tb[1] (RRID:BDSC_55851) (organism)
- w[*]; P{w[+mW.hs]=GawB}how[24B] (RRID:BDSC_1767) (organism)
- w[1118]; P{GD4689}v41136/TM3 (RRID:FlyBase_FBst0463952) (organism)
- w[1118]; P{GD11310}v40512 (RRID:FlyBase_FBst0463603) (organism)
- w[1118]; P{GD4245}v30497 (RRID:FlyBase_FBst0458517) (organism)
- y[1] w[*]; P{w[+mC]=UAS-mCD8::GFP.L}LL5, P{UAS-mCD8::GFP.L}2 (RRID:BDSC_5137) (organism)
- w[1118]; P{GD6741}v17567 (RRID:FlyBase_FBst0452773) (organism)
- w[*]; P{w[+mW.hs]=GawB}D42 (RRID:BDSC_8816) (organism)
Additional research tools detected in this publication
Antibodies used in this publication
- Bruchpilot antibody - Buchner, E.; Universitaetsklinikim Wuerzburg (RRID:AB_2314868)
- p21-activated kinase antibody (RRID:AB_2567913)
- Rhodamine (TRITC)-AffiniPure Rabbit Anti-Horseradish Peroxidase (RRID:AB_2340257)
- Anti-Ubiquitin Antibody (P4D1) (RRID:AB_628423)
- Fluorescein (FITC)-AffiniPure Goat Anti-Horseradish Peroxidase (RRID:AB_2314647)
- Anti-FLAG® M2 Magnetic Beads (RRID:AB_2637089)
- cactus (RRID:AB_2314056)
- c-Myc Antibody (9E10) (RRID:AB_627268)
- Glutamate receptor subunit, DGluR-IIA antibody - Goodman, C.; University of California, Berkeley (RRID:AB_528269)
- UBQLN2 monoclonal antibody (M03), clone 5F5 (RRID:AB_565683)
- Anti-GFP antibody (RRID:AB_300798)
- Mono- and polyubiquitinylated conjugates, mAb (FK2) (RRID:AB_10541840)
- Glutamate receptor IIC antibody (RRID:AB_2568754)
- Glutamate receptor IIB antibody (RRID:AB_2568753)
- futsch antibody - Benzer, S. / Colley, N.; California Institute of Technology (RRID:AB_528403)
- cysteine string protein (CSP), Drosophila common antibody - Buchner, E. / Hofbauer, A.; University of Wuerzburg (RRID:AB_2307345)
- Mouse Anti-Drosophila synapsin Monoclonal Antibody, Unconjugated (RRID:AB_528479)
- Discs large (Drosophila) antibody - Goodman, C.; University of California, Berkeley (RRID:AB_528203)
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RRID:AB_565683
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RRID:AB_10541840
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RRID:AB_528403
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RRID:FlyBase_FBst0458517
Drosophila melanogaster with name w[1118]; P{GD4245}v30497 from Flybase.
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Drosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-mCD8::GFP.L}LL5, P{UAS-mCD8::GFP.L}2 from BDSC.
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RRID:CVCL_Z232
Cell line Schneider 2 is a Spontaneously immortalized cell line with a species of origin Drosophila melanogaster
View all literature mentionsPak[6]/TM3, Sb[1] Ser[1] (organism)
RRID:BDSC_8809
Drosophila melanogaster with name Pak[6]/TM3, Sb[1] Ser[1] from BDSC.
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RRID:BDSC_55851
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RRID:FlyBase_FBst0463952
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RRID:FlyBase_FBst0463603
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RRID:FlyBase_FBst0458517
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Drosophila melanogaster with name w[1118]; P{GD6741}v17567 from Flybase.
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RRID:BDSC_8816
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