論文 - 詳細
| RRC ID | 74745 |
|---|---|
| 著者 | Chen Z, Long H, Guo J, Wang Y, He K, Tao C, Li X, Jiang K, Guo S, Pi Y. |
| タイトル | Autism-Risk Gene necab2 Regulates Psychomotor and Social Behavior as a Neuronal Modulator of mGluR1 Signaling. |
| ジャーナル | Front Mol Neurosci |
| Abstract |
BACKGROUND:De novo deletion of the neuronal calcium-binding protein 2 (NECAB2) locus is associated with idiopathic autism spectrum disorders (ASDs). The in vivo function of NECAB2 in the brain remains largely elusive. METHODS:We investigated the morphological and behavioral profiles of both necab2 knock-out and overexpression zebrafish models. The expression pattern and molecular role of necab2 were probed through a combination of in vitro and in vivo assays. RESULTS:We show that Necab2 is a neuronal specific, cytoplasmic, and membrane-associated protein, abundantly expressed in the telencephalon, habenula, and cerebellum. Necab2 is distributed peri-synaptically in subsets of glutamatergic and GABAergic neurons. CRISPR/Cas9-generated necab2 knock-out zebrafish display normal morphology but exhibit a decrease in locomotor activity and thigmotaxis with impaired social interaction only in males. Conversely, necab2 overexpression yields behavioral phenotypes opposite to the loss-of-function. Proteomic profiling uncovers a role of Necab2 in modulating signal transduction of G-protein coupled receptors. Specifically, co-immunoprecipitation, immunofluorescence, and confocal live-cell imaging suggest a complex containing NECAB2 and the metabotropic glutamate receptor 1 (mGluR1). In vivo measurement of phosphatidylinositol 4,5-bisphosphate further substantiates that Necab2 promotes mGluR1 signaling. CONCLUSIONS:Necab2 regulates psychomotor and social behavior via modulating a signaling cascade downstream of mGluR1. |
| 巻・号 | 15 |
| ページ | 901682 |
| 公開日 | 2022-7-13 |
| DOI | 10.3389/fnmol.2022.901682 |
| PMID | 35909444 |
| PMC | PMC9326220 |
| IF | 4.057 |
| リソース情報 | |
| ゼブラフィッシュ | Tg(vglut2a:loxP-DsRed-loxP-GFP) Tg(gad1b:|R|-GFP) Tg(glyt2:|R|-GFP) |