Regulation of epithelial integrity and organ growth by Tctp and Coracle inDrosophila

Abstract

Author summary Organ growth depends on intercellular signaling for cell proliferation. Accumulating evidence indicates that tissue growth is also regulated by cell junctions. Translationally controlled tumor protein (TCTP) is an evolutionarily conserved protein family implicated in cancer. InDrosophila, Tctp is required for diverse cytoplasmic and nuclear functions including organ growth, DNA repair, and chromatin regulation during development. However, it is unknown whether Tctp plays an additional role in cell junctions at the membrane. Here we show that Tctp localizes together with the FERM domain protein Coracle (Cora) at the basolateral septate junctions in some tissues. Our data suggest that Cora is required for the maintenance of Tctp in the cell membrane but notvice versa. Tctp forms a complex with Cora, and the mutations incoraandTctpgenes show synergistic genetic interaction in the embryo and developing organs. Remarkably, the reduction of Cora and Tctp can induce massive overgrowth in the wing. We propose that the direct interaction of Tctp with the Cora junction complex is required for epithelial integrity and organ growth during development. Regulation of cell junctions is crucial for the integrity of epithelial tissues and organs. Cell junctions also play roles in controlling cell proliferation for organ growth. Translationally controlled tumor protein (TCTP) is a conserved protein involved in growth control, but its role in cell junctions is unknown. Here we show thatDrosophilaTctp directly interacts with the septate junction protein Coracle (Cora) to regulate epithelial integrity and organ growth. Tctp localizes together with Cora in the epidermis of the embryo. Loss of Cora reduces the level of Tctp in the epidermis but notvice versa.cora/+orTctp/+single heterozygotes develop normally to adulthood. However, double heterozygotes forcoraandTctpmutations show severe disruption of epithelia causing synthetic lethality in the embryo. Double knockdown of Cora and Tctp in eye imaginal disc synergistically leads to disruption of the eye disc, resulting in a severe reduction or loss of eye and head. Conversely, double knockdown of Cora and Tctp in wing disc causes overgrowth as well as cell death. Inhibition of cell death under this condition causes hyperplastic growth of the wing disc. Tctp also shows direct and functional interaction with Cora-associated factors like Yurt and Na+/K+-ATPase. This study suggests that proper levels of Tctp and Cora are essential for the maintenance of the Cora complex and the integrity of epithelia. Our data also provide evidence that both Cora and Tctp are required to suppress overgrowth in developing wing.