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果蝇衔接蛋白 Dreadlocks 的精确水平维持生殖环道的大小和稳定性。

Precise levels of the Drosophila adaptor protein Dreadlocks maintain the size and stability of germline ring canals.

机构信息

Department of Biological Sciences, Butler University, Indianapolis, IN 46208, USA.

出版信息

J Cell Sci. 2021 Apr 15;134(8). doi: 10.1242/jcs.254730. Epub 2021 Apr 27.

DOI:10.1242/jcs.254730
PMID:33912915
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8106954/
Abstract

Intercellular bridges are essential for fertility in many organisms. The developing fruit fly egg has become the premier model system to study intercellular bridges. During oogenesis, the oocyte is connected to supporting nurse cells by relatively large intercellular bridges, or ring canals. Once formed, the ring canals undergo a 20-fold increase in diameter to support the movement of materials from the nurse cells to the oocyte. Here, we demonstrate a novel role for the conserved SH2/SH3 adaptor protein Dreadlocks (Dock) in regulating ring canal size and structural stability in the germline. Dock localizes at germline ring canals throughout oogenesis. Loss of Dock leads to a significant reduction in ring canal diameter, and overexpression of Dock causes dramatic defects in ring canal structure and nurse cell multinucleation. The SH2 domain of Dock is required for ring canal localization downstream of Src64 (also known as Src64B), and the function of one or more of the SH3 domains is necessary for the strong overexpression phenotype. Genetic interaction and localization studies suggest that Dock promotes WASp-mediated Arp2/3 activation in order to determine ring canal size and regulate growth. This article has an associated First Person interview with the first author of the paper.

摘要

细胞间桥对于许多生物的生殖力至关重要。发育中的果蝇卵已成为研究细胞间桥的首选模型系统。在卵子发生过程中,卵母细胞通过相对较大的细胞间桥或环管与支持的滋养细胞相连。一旦形成,环管的直径增加 20 倍,以支持物质从滋养细胞向卵母细胞的移动。在这里,我们证明了保守的 SH2/SH3 衔接蛋白 Dreadlocks (Dock) 在调节生殖细胞系中环管大小和结构稳定性方面的新作用。Dock 在卵子发生过程中定位于生殖细胞系的环管。Dock 的缺失导致环管直径显著减小,而过表达 Dock 会导致环管结构和滋养细胞多核化的明显缺陷。Dock 的 SH2 结构域是 Src64(也称为 Src64B)下游环管定位所必需的,一个或多个 SH3 结构域的功能对于强烈的过表达表型是必需的。遗传相互作用和定位研究表明,Dock 促进了 WASp 介导的 Arp2/3 激活,以确定环管的大小并调节生长。本文附有该论文第一作者的相关第一人称采访。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/862410e93852/joces-134-254730-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/d81ca5882762/joces-134-254730-g1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/da0b075acf5f/joces-134-254730-g3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/f29fb7ebdfd9/joces-134-254730-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/ed377c465410/joces-134-254730-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/862410e93852/joces-134-254730-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/d81ca5882762/joces-134-254730-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/e3d48c098155/joces-134-254730-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/da0b075acf5f/joces-134-254730-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/5690f5ccde5e/joces-134-254730-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/f29fb7ebdfd9/joces-134-254730-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/ed377c465410/joces-134-254730-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8106954/862410e93852/joces-134-254730-g7.jpg

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本文引用的文献

1
HtsRC-Mediated Accumulation of F-Actin Regulates Ring Canal Size During Oogenesis.HtsRC 介导的 F-肌动蛋白积累调控卵子发生过程中的环道大小。
Genetics. 2020 Nov;216(3):717-734. doi: 10.1534/genetics.120.303629. Epub 2020 Sep 3.
2
Multivalent nephrin-Nck interactions define a threshold for clustering and tyrosine-dependent nephrin endocytosis.多价足细胞nephrin-Nck 相互作用定义了簇集和依赖酪氨酸的 nephrin 内吞作用的阈值。
J Cell Sci. 2020 Feb 24;133(4):jcs236877. doi: 10.1242/jcs.236877.
3
The Arp2/3 complex and the formin, Diaphanous, are both required to regulate the size of germline ring canals in the developing egg chamber.
Arp2/3 复合物和formin 蛋白 Diaphanous 都需要调节发育中的卵室中的生殖系环道的大小。
Dev Biol. 2020 May 1;461(1):75-85. doi: 10.1016/j.ydbio.2020.01.007. Epub 2020 Jan 13.
4
Targeted substrate degradation by Kelch controls the actin cytoskeleton during ring canal expansion.Kelch 靶向底物降解调控环道扩张过程中的肌动蛋白细胞骨架。
Development. 2019 Jan 2;146(1):dev169219. doi: 10.1242/dev.169219.
5
The Misshapen kinase regulates the size and stability of the germline ring canals in the Drosophila egg chamber.畸形激酶调节果蝇卵室中生殖系环管的大小和稳定性。
Dev Biol. 2018 Aug 15;440(2):99-112. doi: 10.1016/j.ydbio.2018.05.006. Epub 2018 May 9.
6
Subcellular Specialization and Organelle Behavior in Germ Cells.生殖细胞的亚细胞特化和细胞器行为。
Genetics. 2018 Jan;208(1):19-51. doi: 10.1534/genetics.117.300184.
7
Automatic stage identification of Drosophila egg chamber based on DAPI images.基于DAPI图像的果蝇卵室自动阶段识别
Sci Rep. 2016 Jan 6;6:18850. doi: 10.1038/srep18850.
8
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Proc Natl Acad Sci U S A. 2015 Oct 13;112(41):12717-22. doi: 10.1073/pnas.1504455112. Epub 2015 Sep 30.
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Genetics. 2015 Nov;201(3):1117-31. doi: 10.1534/genetics.115.181289. Epub 2015 Sep 16.
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