Molecular and functional characterization of an evolutionarily conserved CREB-binding protein in the Lymnaea CNS

Dai Hatakeyama*, Hiroshi Sunada, Yuki Totani, Takayuki Watanabe, Ildikó Felletár, Adam Fitchett, Murat Eravci, Aikaterini Anagnostopoulou, Ryosuke Miki, Ayano Okada, Naoya Abe, Takashi Kuzuhara, Ildikó Kemenes, Etsuro Ito, György Kemenes*

*この研究の対応する著者

研究成果: Article査読

7 被引用数 (Scopus)

抄録

In eukaryotes, CREB-binding protein (CBP), a coactivator of CREB, functions both as a platform for recruiting other components of the transcriptional machinery and as a histone acetyltransferase (HAT) that alters chromatin structure. We previously showed that the transcriptional activity of cAMP-responsive element binding protein (CREB) plays a crucial role in neuronal plasticity in the pond snail Lymnaea stagnalis. However, there is no information on the molecular structure and HAT activity of CBP in the Lymnaea central nervous system (CNS), hindering an investigation of its postulated role in long-term memory (LTM). Here, we characterize the Lymnaea CBP (LymCBP) gene and identify a conserved domain of LymCBP as a functional HAT. Like CBPs of other species, LymCBP possesses functional domains, such as the KIX domain, which is essential for interaction with CREB and was shown to regulate LTM. In-situ hybridization showed that the staining patterns of LymCBP mRNA in CNS are very similar to those of Lymnaea CREB1. A particularly strong LymCBP mRNA signal was observed in the cerebral giant cell (CGC), an identified extrinsic modulatory interneuron of the feeding circuit, the key to both appetitive and aversive LTM for taste. Biochemical experiments using the recombinant protein of the LymCBP HAT domain showed that its enzymatic activity was blocked by classical HAT inhibitors. Preincubation of the CNS with such inhibitors blocked cAMP-induced synaptic facilitation between the CGC and an identified follower motoneuron of the feeding system. Taken together, our findings suggest a role for the HAT activity of LymCBP in synaptic plasticity in the feeding circuitry.

本文言語English
論文番号e22593
ジャーナルFASEB Journal
36
11
DOI
出版ステータスPublished - 2022 11月

ASJC Scopus subject areas

  • バイオテクノロジー
  • 生化学
  • 分子生物学
  • 遺伝学

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