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Blockade of Smad4 SUMOylation impairs spatial learning and memory in rats
Author(s) -
Lee HsiaoYuan,
Hsu WeiLun,
Ma YunLi
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1284.5
Subject(s) - sumo protein , barnes maze , gene knockdown , hippocampus , ubiquitin ligase , hippocampal formation , neuroscience , biology , chemistry , microbiology and biotechnology , spatial learning , ubiquitin , cell culture , gene , genetics
We have previously found that the protein inhibitor of activated STAT1 ( pias1 ) gene is differentially expressed between fast learners and slow learners from the water maze learning task with fast learners showing a higher expression level of pias1 in hippocampal neurons. Spatial training also increases PIAS1 expression in rat CA1 area. Further, overexpression of PIAS1 in CA1 neurons enhances whereas knockdown of PIAS1 impairs spatial learning and memory performance in rats. Because PIAS1 is a transcriptional regulator that possesses small ubiquitin‐like modifier (SUMO) E3 ligase activity, in this study, we aimed to examine the mechanism underlying PIAS1‐mediated learning and memory facilitation. Smad4 is a downstream target of transforming growth factor‐beta signaling. Smad4 has been well studied in the immune system, but its role in the brain has been rarely examined. In this study we examined whether Smad4 could be SUMO‐modified by PIAS1 in the brain and whether Smad4 SUMOylation plays a role in spatial learning and memory formation. Our results showed that Smad4 could be SUMO‐modified by PIAS1 at Lys‐113 and Lys‐159 both in cell lines and in rat hippocampus in vivo . Further, water maze training increased the level of Smad4 SUMOylation in CA1 neurons compared with the swim controls. Smad4 SUMOylation is also induced by neuronal activation. On the other hand, transduction of the lenti‐Smad4WT vector did not apparently affect spatial learning and memory, but transduction of the lenti‐Smad4 sumo‐mutant vector (Smad4K113RK159R) significantly impaired spatial learning and memory performance. In future studies, we will identify the downstream genes that are regulated by Smad4 SUMOylation and are involved in spatial learning and memory formation. Support or Funding Information This work was supported by Grant No. MOST104‐2320‐B‐001‐002‐MY3 from Taiwan.