Keramidioti Athina, Golegou Evgenia, Psarra Eleni, Paschalidis Nikolaos, Kalodimou Konstantina, Yamamoto Shinya, Delidakis Christos, Vakaloglou Katerina M, Zervas Christos G
Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
Front Cell Dev Biol. 2022 Dec 1;10:951082. doi: 10.3389/fcell.2022.951082. eCollection 2022.
Integrins are the major family of transmembrane proteins that mediate cell-matrix adhesion and have a critical role in epithelial morphogenesis. Integrin function largely depends on the indirect connection of the integrin cytoplasmic tail to the actin cytoskeleton through an intracellular protein network, the integrin adhesome. What is currently unknown is the role of individual integrin adhesome components in epithelia dynamic reorganization. egg chamber consists of the oocyte encircled by a monolayer of somatic follicle epithelial cells that undergo specific cell shape changes. Egg chamber morphogenesis depends on a developmental array of cell-cell and cell-matrix signalling events. Recent elegant work on the role of integrins in the egg chamber has indicated their essential role in the early stages of oogenesis when the pre-follicle cells assemble into the follicle epithelium. Here, we have focused on the functional requirement of two key integrin adhesome components, Parvin and Integrin-Linked Kinase (ILK). Both proteins are expressed in the developing ovary from pupae to the adult stage and display enriched expression in terminal filament and stalk cells, while their genetic removal from early germaria results in severe disruption of the subsequent oogenesis, leading to female sterility. Combining genetic mosaic analysis of available null alleles for both and with conditional rescue utilizing the UAS/Gal4 system, we found that Parvin and ILK are required in pre-follicle cells for germline cyst encapsulation and stalk cell morphogenesis. Collectively, we have uncovered novel developmental functions for both Parvin and ILK, which closely synergize with integrins in epithelia.
整合素是介导细胞与基质黏附的主要跨膜蛋白家族,在上皮形态发生中起关键作用。整合素的功能很大程度上依赖于通过细胞内蛋白网络(整合素黏附体)将整合素细胞质尾部与肌动蛋白细胞骨架间接连接。目前尚不清楚的是单个整合素黏附体成分在上皮动态重组中的作用。卵室由被单层体细胞卵泡上皮细胞包围的卵母细胞组成,这些体细胞会发生特定的细胞形状变化。卵室形态发生依赖于一系列细胞间和细胞与基质的信号转导事件。最近关于整合素在卵室中作用的出色研究表明,它们在卵泡前体细胞组装成卵泡上皮的卵子发生早期阶段起着至关重要的作用。在这里,我们重点研究了整合素黏附体的两个关键成分——Parvin和整合素连接激酶(ILK)的功能需求。这两种蛋白在从蛹期到成虫期的发育卵巢中均有表达,并且在端丝和柄细胞中表达丰富,而从早期生殖腺中基因敲除它们会导致随后卵子发生的严重破坏,导致雌性不育。利用UAS/Gal4系统,将对两者可用无效等位基因的遗传镶嵌分析与条件性拯救相结合,我们发现Parvin和ILK在卵泡前体细胞中对于生殖系囊肿包封和柄细胞形态发生是必需的。总的来说,我们发现了Parvin和ILK的新的发育功能,它们在上皮中与整合素密切协同作用。