Increased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic mice

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number39
JournalMolecular brain
Volume14
Issue number1
DOIs
Publication statusPublished - 2021 Dec

Keywords

  • Protein synthesis
  • Ribosomal protein
  • Shank3
  • Striatum
  • Synaptosome

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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