Shin-Haw Lee, Sina Hadipour-Lakmehsari, Anthony O Gramolini
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引用次数: 2
摘要
肌内质网(sarco-endoplasmic reticulum, SR/ER)是真核细胞中最大的膜结合细胞器,在细胞基本过程和许多心脏疾病的发生进展中起着重要作用。然而,其结构组织的许多方面在很大程度上仍然未知,特别是在具有高度分化的SR/ER网络的细胞中。在Lee等人最近发表的一项研究中(Nat comm 11(1):965),我们报道了心脏富集的SR/ER膜蛋白REEP5,该蛋白主要参与调节心肌细胞SR/ER组织和细胞应激反应。在体外小鼠心肌细胞中,REEP5缺失导致SR/ER膜不稳定和腔内空泡化,同时心肌细胞收缩性降低和Ca2+循环中断。此外,在体内,CRISPR/ cas9介导的REEP5功能丧失斑马鱼突变体在短期维拉帕米治疗后对心力衰竭诱导表现出敏感的心功能障碍。此外,体内腺相关病毒(AAV9)诱导的小鼠REEP5耗竭表现为心功能障碍,心室扩张,心脏纤维化增加,射血分数降低。这些结果证明了REEP5在SR/ER组织和功能中的关键作用。
Towards understanding the role of Receptor Expression Enhancing Protein 5 (REEP5) in cardiac muscle and beyond.
The sarco-endoplasmic reticulum (SR/ER) is the largest membrane-bound organelle in eukaryotic cells and plays important roles in essential cellular processes, and in development and progression of many cardiac diseases. However, many aspects of its structural organization remain largely unknown, particularly in cells with a highly differentiated SR/ER network. In a recently published study led by Lee et al. (Nat Commun 11(1):965), we reported a cardiac enriched SR/ER membrane protein REEP5 that is centrally involved in regulating SR/ER organization and cellular stress responses in cardiac myocytes. In vitro REEP5 depletion in mouse cardiac myocytes resulted in SR/ER membrane destabilization and luminal vacuolization along with decreased myocyte contractility and disrupted Ca2+ cycling. Further, in vivo CRISPR/Cas9-mediated REEP5 loss-of-function zebrafish mutants showed sensitized cardiac dysfunction to heart failure induction upon short-term verapamil treatment. Additionally, in vivo adeno-associated viral (AAV9)-induced REEP5 depletion in the mouse demonstrated cardiac dysfunction with dilated cardiac chambers, increased cardiac fibrosis, and reduced ejection fraction. These results demonstrate the critical role of REEP5 in SR/ER organization and function.
Cell StressBiochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍:
Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging.
The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.