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Select Septate Junction Proteins Direct ROS-Mediated Paracrine Regulation of Drosophila Cardiac Function.

ABSTRACT: Septate junction (SJ) complex proteins act in unison to provide a paracellular barrier and maintain structural integrity. Here, we identify a non-barrier role of two individual SJ proteins, Coracle (Cora) and Kune-kune (Kune). Reactive oxygen species (ROS)-p38 MAPK signaling in non-myocytic pericardial cells (PCs) is important for maintaining normal cardiac physiology in Drosophila. However, the underlying mechanisms remain unknown. We find that in PCs, Cora and Kune are altered in abundance in response to manipulations of ROS-p38 signaling. Genetic analyses establish Cora and Kune as key effectors of ROS-p38 signaling in PCs on proper heart function. We further determine that Cora regulates normal Kune levels in PCs, which in turn modulates normal Kune levels in the cardiomyocytes essential for proper heart function. Our results thereby reveal select SJ proteins Cora and Kune as signaling mediators of the PC-derived ROS regulation of cardiac physiology.

SUBMITTER: Lim HY

PROVIDER: S-EPMC6703176 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Select Septate Junction Proteins Direct ROS-Mediated Paracrine Regulation of Drosophila Cardiac Function.

Lim Hui-Ying HY Bao Hong H Liu Ying Y Wang Weidong W

Cell reports 20190801 6

Septate junction (SJ) complex proteins act in unison to provide a paracellular barrier and maintain structural integrity. Here, we identify a non-barrier role of two individual SJ proteins, Coracle (Cora) and Kune-kune (Kune). Reactive oxygen species (ROS)-p38 MAPK signaling in non-myocytic pericardial cells (PCs) is important for maintaining normal cardiac physiology in Drosophila. However, the underlying mechanisms remain unknown. We find that in PCs, Cora and Kune are altered in abundance in ...[more]

PMID: 31390561

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Project description:Protein components of the invertebrate occluding junction-known as the septate junction (SJ) - are required for morphogenetic developmental events during embryogenesis in Drosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell migration. We found that all four SJ proteins are expressed in egg chambers throughout oogenesis, with the highest and most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 10B. SJ protein relocalization requires the expression of other SJ proteins, as well as Rab5 and Rab11 in a manner similar to SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the border cell cluster results in border cell migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggests that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages. Article Summary: Septate junction (SJ) proteins are essential for forming an occluding junction in epithelial tissues in Drosophila melanogaster, and also for morphogenetic events that occur prior to the formation of the junction during embryogenesis. Here we show that SJ proteins are expressed in the follicular epithelium of egg chambers during oogenesis and are required for morphogenetic events including egg elongation, dorsal appendages formation, and border cell migration. Additionally, the formation of SJs during oogenesis is similar to that in embryonic epithelia.

Dataset Information

Select Septate Junction Proteins Direct ROS-Mediated Paracrine Regulation of Drosophila Cardiac Function.

Publications

Select Septate Junction Proteins Direct ROS-Mediated Paracrine Regulation of Drosophila Cardiac Function.

Similar Datasets

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