Knowledge Resource Center for Ecological Environment in Arid Area
| DOI | 10.1016/j.molmet.2022.101542 |
| Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells | |
| Greenwood, Mingkwan; Gillard, Benjamin T.; Farrukh, Rizwan; Paterson, Alex; Althammer, Ferdinand; Grinevich, Valery; Murphy, David; Greenwood, Michael P. | |
| 通讯作者 | Greenwood, MP |
| 来源期刊 | MOLECULAR METABOLISM
 |
| ISSN | 2212-8778 |
| 出版年 | 2022 |
| 卷号 | 63 |
| 英文摘要 | Objectives: Dynamic changes to neuropeptide hormone synthesis and secretion by hypothalamic neuroendocrine cells is essential to ensure metabolic homeostasis. The specialised molecular mechanisms that allow neuroendocrine cells to synthesise and secrete vast quantities of neuropeptides remain ill defined. The objective of this study was to identify novel genes and pathways controlled by transcription factor and endoplasmic reticulum stress sensor Creb3l1 which is robustly activated in hypothalamic magnocellular neurones in response to increased demand for protein synthesis. Methods: We adopted a multiomic strategy to investigate specific roles of Creb3l1 in rat magnocellular neurones. We first performed chromatin immunoprecipitation followed by genome sequencing (ChIP-seq) to identify Creb3l1 genomic targets and then integrated this data with RNA sequencing data from physiologically stimulated and Creb3l1 knockdown magnocellular neurones. Results: The data converged on Creb3l1 targets that code for ribosomal proteins and endoplasmic reticulum proteins crucial for the maintenance of cellular proteostasis. We validated genes that compose the PERK arm of the unfolded protein response pathway including Eif2ak3, Eif2s1, Atf4 and Ddit3 as direct Creb3l1 targets. Importantly, knockdown of Creb3l1 in the hypothalamus led to a dramatic depletion in neuropeptide synthesis and secretion. The physiological outcomes from studies of paraventricular and supraoptic nuclei Creb3l1 knockdown animals were changes to food and water consumption. Conclusion: Collectively, our data identify Creb3l1 as a comprehensive controller of the PERK signalling pathway in magnocellular neurones in response to physiological stimulation. The broad regulation of neuropeptide synthesis and secretion by Creb3l1 presents a new therapeutic strategy for metabolic diseases. (c) 2022 The Author(s). Published by Elsevier GmbH. |
| 英文关键词 | Unfolded protein response Endoplasmic reticulum stress Ribosome Neuropeptide Hypothalamus PERK |
| 类型 | Article |
| 语种 | 英语 |
| 开放获取类型 | gold, Green Published |
| 收录类别 | SCI-E |
| WOS记录号 | WOS:000839463200002 |
| WOS关键词 | UNFOLDED PROTEIN RESPONSE ; GENE-EXPRESSION ; PARAVENTRICULAR NUCLEUS ; CREB/ATF-FAMILY ; OASIS ; OXYTOCIN ; NEURONS ; KINASE ; CLEAVAGE ; PATHWAY |
| WOS类目 | Endocrinology & Metabolism |
| WOS研究方向 | Endocrinology & Metabolism |
| 资源类型 | 期刊论文 |
| 条目标识符 | http://119.78.100.177/qdio/handle/2XILL650/393812 |
| 推荐引用方式 GB/T 7714 | Greenwood, Mingkwan,Gillard, Benjamin T.,Farrukh, Rizwan,et al. Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells[J],2022,63. |
| APA | Greenwood, Mingkwan.,Gillard, Benjamin T..,Farrukh, Rizwan.,Paterson, Alex.,Althammer, Ferdinand.,...&Greenwood, Michael P..(2022).Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells.MOLECULAR METABOLISM,63. |
| MLA | Greenwood, Mingkwan,et al."Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells".MOLECULAR METABOLISM 63(2022). |
| 条目包含的文件 | 条目无相关文件。 | |||||
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。
