Cul4 ubiquitin ligase cofactor DCAF12 promotes neurotransmitter release and homeostatic plasticity

Lilian A. Patrón, Kei Nagatomo, David Tyler Eves, Mays Imad, Kimberly Young, Meaghan Torvund, Xiufang Guo, Gregory C. Rogers, Konrad E Zinsmaier

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)993-1010
Number of pages18
JournalJournal of Cell Biology
Volume218
Issue number3
DOIs
StatePublished - Mar 1 2019

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Neuromuscular Junction
Ligases
Ubiquitin
Neurotransmitter Agents
Drosophila
Neuronal Plasticity
Ubiquitination
Presynaptic Terminals
Glutamate Receptors
Motor Neurons
Locomotion
Axons
Down-Regulation
Muscles

ASJC Scopus subject areas

  • Cell Biology

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Cul4 ubiquitin ligase cofactor DCAF12 promotes neurotransmitter release and homeostatic plasticity. / Patrón, Lilian A.; Nagatomo, Kei; Eves, David Tyler; Imad, Mays; Young, Kimberly; Torvund, Meaghan; Guo, Xiufang; Rogers, Gregory C.; Zinsmaier, Konrad E.

In: Journal of Cell Biology, Vol. 218, No. 3, 01.03.2019, p. 993-1010.

Research output: Contribution to journalArticle

Patrón, Lilian A. ; Nagatomo, Kei ; Eves, David Tyler ; Imad, Mays ; Young, Kimberly ; Torvund, Meaghan ; Guo, Xiufang ; Rogers, Gregory C. ; Zinsmaier, Konrad E. / Cul4 ubiquitin ligase cofactor DCAF12 promotes neurotransmitter release and homeostatic plasticity. In: Journal of Cell Biology. 2019 ; Vol. 218, No. 3. pp. 993-1010.
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AU - Eves, David Tyler

AU - Imad, Mays

AU - Young, Kimberly

AU - Torvund, Meaghan

AU - Guo, Xiufang

AU - Rogers, Gregory C.

AU - Zinsmaier, Konrad E

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