Increased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic mice
Abstract The SH3 and multiple ankyrin repeat domains 3 (Shank3) protein is a core organizer of the macromolecular complex in excitatory postsynapses, and its defects cause numerous synaptopathies, including autism spectrum disorders. Although the function of Shank3 as a postsynaptic scaffold is adeq...
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | Molecular Brain |
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| Online Access: | https://doi.org/10.1186/s13041-021-00756-z |
| _version_ | 1830083906485878784 |
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| author | Chunmei Jin Yeunkum Lee Hyojin Kang Kwon Jeong Joori Park Yinhua Zhang Hyae Rim Kang Ruiying Ma Hyunyoung Seong Yoonhee Kim Hosung Jung Jin Young Kim Yoon Ki Kim Kihoon Han |
| author_facet | Chunmei Jin Yeunkum Lee Hyojin Kang Kwon Jeong Joori Park Yinhua Zhang Hyae Rim Kang Ruiying Ma Hyunyoung Seong Yoonhee Kim Hosung Jung Jin Young Kim Yoon Ki Kim Kihoon Han |
| author_sort | Chunmei Jin |
| collection | DOAJ |
| description | Abstract The SH3 and multiple ankyrin repeat domains 3 (Shank3) protein is a core organizer of the macromolecular complex in excitatory postsynapses, and its defects cause numerous synaptopathies, including autism spectrum disorders. Although the function of Shank3 as a postsynaptic scaffold is adequately established, other potential mechanisms through which Shank3 broadly modulates the postsynaptic proteome remain relatively unexplored. In our previous quantitative proteomic analysis, six up-regulated ribosomal proteins were identified in the striatal synaptosome of Shank3-overexpressing transgenic (TG) mice. In the present study, we validated the increased levels of RPLP1 and RPL36A in synaptosome, but not in whole lysate, of the TG striatum. Moreover, protein synthesis and extracellular signaling-regulated kinase (ERK) activity were enhanced in the TG striatal synaptosome. To understand the potential contribution of increased protein synthesis to the proteomic change in the TG striatal synaptosome, we performed RNA-sequencing analyses on both whole synaptosomal and synaptic polysome-enriched fractions. Comparative analyses showed a positive correlation only between the polysome-associated transcriptome and up-regulated proteome in the TG striatal synaptosome. Our findings suggest a novel mechanism through which Shank3 may remodel the postsynaptic proteome by regulating synaptic protein synthesis, whose dysfunction can be implicated in SHANK3-associated synaptopathies. |
| first_indexed | 2024-12-14T16:31:55Z |
| format | Article |
| id | doaj.art-a5d01e752d3f48ab8b849fd86580ad31 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-14T16:31:55Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-a5d01e752d3f48ab8b849fd86580ad312022-12-21T22:54:34ZengBMCMolecular Brain1756-66062021-02-011411510.1186/s13041-021-00756-zIncreased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic miceChunmei Jin0Yeunkum Lee1Hyojin Kang2Kwon Jeong3Joori Park4Yinhua Zhang5Hyae Rim Kang6Ruiying Ma7Hyunyoung Seong8Yoonhee Kim9Hosung Jung10Jin Young Kim11Yoon Ki Kim12Kihoon Han13Department of Neuroscience, College of Medicine, Korea UniversityDepartment of Neuroscience, College of Medicine, Korea UniversityDivision of National Supercomputing, Korea Institute of Science and Technology Information (KISTI)Creative Research Initiatives Center for Molecular Biology of Translation, Korea UniversityCreative Research Initiatives Center for Molecular Biology of Translation, Korea UniversityDepartment of Neuroscience, College of Medicine, Korea UniversityDepartment of Neuroscience, College of Medicine, Korea UniversityDepartment of Neuroscience, College of Medicine, Korea UniversityDepartment of Neuroscience, College of Medicine, Korea UniversityDepartment of Neuroscience, College of Medicine, Korea UniversityBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of MedicineResearch Center for Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Creative Research Initiatives Center for Molecular Biology of Translation, Korea UniversityDepartment of Neuroscience, College of Medicine, Korea UniversityAbstract The SH3 and multiple ankyrin repeat domains 3 (Shank3) protein is a core organizer of the macromolecular complex in excitatory postsynapses, and its defects cause numerous synaptopathies, including autism spectrum disorders. Although the function of Shank3 as a postsynaptic scaffold is adequately established, other potential mechanisms through which Shank3 broadly modulates the postsynaptic proteome remain relatively unexplored. In our previous quantitative proteomic analysis, six up-regulated ribosomal proteins were identified in the striatal synaptosome of Shank3-overexpressing transgenic (TG) mice. In the present study, we validated the increased levels of RPLP1 and RPL36A in synaptosome, but not in whole lysate, of the TG striatum. Moreover, protein synthesis and extracellular signaling-regulated kinase (ERK) activity were enhanced in the TG striatal synaptosome. To understand the potential contribution of increased protein synthesis to the proteomic change in the TG striatal synaptosome, we performed RNA-sequencing analyses on both whole synaptosomal and synaptic polysome-enriched fractions. Comparative analyses showed a positive correlation only between the polysome-associated transcriptome and up-regulated proteome in the TG striatal synaptosome. Our findings suggest a novel mechanism through which Shank3 may remodel the postsynaptic proteome by regulating synaptic protein synthesis, whose dysfunction can be implicated in SHANK3-associated synaptopathies.https://doi.org/10.1186/s13041-021-00756-zShank3Ribosomal proteinProtein synthesisStriatumSynaptosome |
| spellingShingle | Chunmei Jin Yeunkum Lee Hyojin Kang Kwon Jeong Joori Park Yinhua Zhang Hyae Rim Kang Ruiying Ma Hyunyoung Seong Yoonhee Kim Hosung Jung Jin Young Kim Yoon Ki Kim Kihoon Han Increased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic mice Molecular Brain Shank3 Ribosomal protein Protein synthesis Striatum Synaptosome |
| title | Increased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic mice |
| title_full | Increased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic mice |
| title_fullStr | Increased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic mice |
| title_full_unstemmed | Increased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic mice |
| title_short | Increased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic mice |
| title_sort | increased ribosomal protein levels and protein synthesis in the striatal synaptosome of shank3 overexpressing transgenic mice |
| topic | Shank3 Ribosomal protein Protein synthesis Striatum Synaptosome |
| url | https://doi.org/10.1186/s13041-021-00756-z |
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