Shank3 regulates striatal synaptic abundance of Cyld, a deubiquitinase specific for Lys63‐linked polyubiquitin chains
| Autor: | Kihoon Han, Yoonhee Kim, Jin Young Kim, Yinhua Zhang, Chunmei Jin, Yeunkum Lee, Ki Na Yun, Shinhyun Kim, Hyojin Kang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Proteomics
0301 basic medicine Transgene Mice Transgenic Nerve Tissue Proteins Striatum Biology Biochemistry Interactome Deubiquitinating enzyme Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Ubiquitin Animals Polyubiquitin Mice Knockout Microfilament Proteins Ubiquitination Corpus Striatum Deubiquitinating Enzyme CYLD Cell biology Mice Inbred C57BL 030104 developmental biology Synapses Excitatory postsynaptic potential biology.protein Ankyrin repeat Postsynaptic density 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurochemistry. 150:776-786 |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | The SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins are core organizers of the postsynaptic density in neuronal excitatory synapses, and their defects cause various neurodevelopmental and neuropsychiatric disorders. Mechanistically, Shank3 directly and indirectly interacts with hundreds of synaptic proteins with diverse functions and potentially exerts its regulatory roles in synaptic development and function via these interactors. However, Shank3-dependent regulation of synaptic abundance has been validated in vivo for only a few Shank3 interactors. Here, using a quantitative proteomic analysis, we identified 136 proteins with altered synaptic abundance in the striatum of Shank3-overexpressing transgenic (TG) mice. By comparing these proteins with those found in a previous analysis of the postsynaptic density of Shank3 knock-out (KO) striatum, we identified and confirmed that cylindromatosis-associated deubiquitinase (Cyld), a deubiquitinase specific for Lys63-linked polyubiquitin chains, was up- and down-regulated in Shank3 TG and KO striatal synapses, respectively. Consistently, we found that the synaptic levels of Lys63-linked polyubiquitin chains were down- and up-regulated in the Shank3 TG and KO striata, respectively. Furthermore, by isolating and analyzing the synaptic Cyld complex, we generated a Cyld interactome consisting of 103 proteins, which may include Cyld substrates. Bioinformatic analyses suggested associations of the Cyld interactome with a few brain disorders and synaptic functions. Taken together, these results suggest that Shank3 regulates the synaptic abundance of Cyld in the mouse striatum and, thereby, potentially modulates the Lys63-linked polyubiquitination of striatal synaptic proteins. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text