TY - JOUR
T1 - Cul4 ubiquitin ligase cofactor DCAF12 promotes neurotransmitter release and homeostatic plasticity
AU - Patrón, Lilian A.
AU - Nagatomo, Kei
AU - Eves, David Tyler
AU - Imad, Mays
AU - Young, Kimberly
AU - Torvund, Meaghan
AU - Guo, Xiufang
AU - Rogers, Gregory C.
AU - Zinsmaier, Konrad E.
N1 - Funding Information:
This work was supported by grants from National Institute of Neurological Disorders and Stroke (R03 NS057215) and National Science Foundation (IOS-1121054 to K.E. Zinsmaier). The authors declare no competing financial interests.
Funding Information:
We thank Drs. Cheng-Ting Chien (Academia Sinica, Taiwan), Aaron DiAntonio, Hugo Bellen, Stephan Sigrist, Jacob Seeler (Institut Pasteur, Paris, France), Carl-Henrik Heldin, Joseph Gall (Carnegie Institution for Science, Washington, DC), Edward Giniger (National Institute of Neurological Disorders and Stroke, Bethesda, MD), C. Andrew Frank, Robert Duronio, the Developmental Studies Hybridoma Bank at the University of Iowa, the Genomics Resource Center at Indiana University (supported by National Institutes of Health grant 2P40OD010949), and the Exelixis Collection at the Harvard Medical School for antibodies and/or fly strains. We thank Patty Jansma, Andrea Wellington, Jinhui Zhang, Mirka Honkanen, and Milos Babic for their technical help and critical feedback.
Publisher Copyright:
© 2019 Patrón et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license
PY - 2019/3/1
Y1 - 2019/3/1
N2 - We genetically characterized the synaptic role of the Drosophila homologue of human DCAF12, a putative cofactor of Cullin4 (Cul4) ubiquitin ligase complexes. Deletion of Drosophila DCAF12 impairs larval locomotion and arrests development. At larval neuromuscular junctions (NMJs), DCAF12 is expressed presynaptically in synaptic boutons, axons, and nuclei of motor neurons. Postsynaptically, DCAF12 is expressed in muscle nuclei and facilitates Cul4-dependent ubiquitination. Genetic experiments identified several mechanistically independent functions of DCAF12 at larval NMJs. First, presynaptic DCAF12 promotes evoked neurotransmitter release. Second, postsynaptic DCAF12 negatively controls the synaptic levels of the glutamate receptor subunits GluRIIA, GluRIIC, and GluRIID. The down-regulation of synaptic GluRIIA subunits by nuclear DCAF12 requires Cul4. Third, presynaptic DCAF12 is required for the expression of synaptic homeostatic potentiation. We suggest that DCAF12 and Cul4 are critical for normal synaptic function and plasticity at larval NMJs.
AB - We genetically characterized the synaptic role of the Drosophila homologue of human DCAF12, a putative cofactor of Cullin4 (Cul4) ubiquitin ligase complexes. Deletion of Drosophila DCAF12 impairs larval locomotion and arrests development. At larval neuromuscular junctions (NMJs), DCAF12 is expressed presynaptically in synaptic boutons, axons, and nuclei of motor neurons. Postsynaptically, DCAF12 is expressed in muscle nuclei and facilitates Cul4-dependent ubiquitination. Genetic experiments identified several mechanistically independent functions of DCAF12 at larval NMJs. First, presynaptic DCAF12 promotes evoked neurotransmitter release. Second, postsynaptic DCAF12 negatively controls the synaptic levels of the glutamate receptor subunits GluRIIA, GluRIIC, and GluRIID. The down-regulation of synaptic GluRIIA subunits by nuclear DCAF12 requires Cul4. Third, presynaptic DCAF12 is required for the expression of synaptic homeostatic potentiation. We suggest that DCAF12 and Cul4 are critical for normal synaptic function and plasticity at larval NMJs.
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U2 - 10.1083/jcb.201805099
DO - 10.1083/jcb.201805099
M3 - Article
C2 - 30670470
AN - SCOPUS:85062419659
SN - 0021-9525
VL - 218
SP - 993
EP - 1010
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 3
ER -