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在秀丽隐杆线虫中对Rab GTPase基因进行的RNA干扰筛选表明,在生殖系统的体细胞中,形态发生对rab-1的需求高于干细胞微环境维持。

An RNAi screen of Rab GTPase genes in Caenorhabditis elegans reveals that morphogenesis has a higher demand than stem cell niche maintenance for rab-1 in the somatic cells of the reproductive system.

作者信息

Singh Noor, Scott Kayt, Proctor Jayce, Gordon Kacy Lynn

机构信息

Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

出版信息

G3 (Bethesda). 2025 Jun 4;15(6). doi: 10.1093/g3journal/jkaf085.

Abstract

Membrane trafficking is a crucial function of all cells and is regulated at multiple levels from vesicle formation, packaging, and localization to fusion, exocytosis, and endocytosis. Rab GTPase proteins are core regulators of eukaryotic membrane trafficking, but developmental roles of specific Rab GTPases are less well characterized, potentially because of their essentiality for basic cellular function. Caenorhabditis elegans gonad development entails the coordination of cell growth, proliferation, and migration-processes in which membrane trafficking is known to be required. Here, we take an organ-focused approach to Rab GTPase function in vivo to assess the roles of Rab genes in reproductive system development. We performed a whole-body RNAi screen of the entire Rab family in C. elegans to uncover Rabs essential for gonad development. Notable gonad defects resulted from RNAi knockdown of rab-1, the key regulator of ER-Golgi trafficking. We then examined the effects of tissue-specific RNAi knockdown of rab-1 in somatic reproductive system and germline cells. We interrogated the dual functions of the distal tip cell as both a leader cell of gonad organogenesis and the germline stem cell niche. We find that rab-1 functions cell-autonomously and non-cell-autonomously to regulate both somatic gonad and germline development. Gonad migration, elongation, and gamete differentiation-but surprisingly not germline stem niche function-are highly sensitive to rab-1 RNAi.

摘要

膜运输是所有细胞的一项关键功能,并且在从囊泡形成、包装、定位到融合、胞吐作用和内吞作用的多个层面受到调控。Rab GTPase蛋白是真核细胞膜运输的核心调节因子,但特定Rab GTPase的发育作用尚未得到充分表征,这可能是因为它们对基本细胞功能至关重要。秀丽隐杆线虫性腺发育需要协调细胞生长、增殖和迁移过程,而这些过程已知需要膜运输。在这里,我们采用以器官为重点的方法来研究Rab GTPase在体内的功能,以评估Rab基因在生殖系统发育中的作用。我们对秀丽隐杆线虫的整个Rab家族进行了全身RNA干扰筛选,以发现性腺发育所必需的Rab。对ER-高尔基体运输的关键调节因子rab-1进行RNA干扰敲低导致了明显的性腺缺陷。然后,我们研究了在体细胞生殖系统和生殖系细胞中对rab-1进行组织特异性RNA干扰敲低的影响。我们探究了远端末梢细胞作为性腺器官发生的引导细胞和生殖系干细胞微环境的双重功能。我们发现rab-1以细胞自主和非细胞自主的方式发挥作用,以调节体细胞性腺和生殖系的发育。性腺迁移、伸长和配子分化——但令人惊讶的是生殖系干细胞微环境功能不受影响——对rab-1 RNA干扰高度敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f7/12135009/ff22e860bde7/jkaf085f1.jpg

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