Tctp interacts with septate junction protein Coracle to regulate epithelial integrity and organ growth in Drosophila

Abstract

Junctional organization of epithelial cells is crucial for the maintenance of tissues and organs. Cell junction proteins are also involved in controlling cell proliferation in developing organs. Translationally controlled tumor protein (TCTP) is a family of conserved proteins implicated in development and cancer, but its role in cell junctions is unknown. Here we show that Drosophila Tctp forms a protein complex with the FERM domain protein Coracle (Cora), a septate junction protein involved in epithelial integrity and cell proliferation. Tctp and cora show synergistic genetic interaction in a tissue-specific manner. In embryo, genetic interaction between Tctp$^{h59}$/+ and cora$^4$/+ heterozygotes causes synthetic lethality with epithelial disruption. Cora is required for junctional localization of Tctp in embryonic epidermis. Double knockdown of Tctp and Cora in eye imaginal disc results in complete loss of eye and head in contrast to mild effects of single knockdown. On the contrary, double knockdown of Tctp and Cora in wing disc induces tissue overgrowth with accumulation of F-actin. Tctp also functions together with Cora-associated septate junction proteins Yurt and Na$^+$/K$^+$-ATPase. This study provides evidence that Tctp and Cora form a novel junctional complex to maintain the integrity of embryonic epithelia and act to promote or suppress growth in an organ-specific manner.