Biology

Dr. K. Venkatesan Iyer
Max Planck Institute for Molecular Cell Biology and Genetics.

Epithelial tissues comprise majority of tissues in our body and about 70-80 % of all cancers are of epithelial origin. These tissues are dynamically remodelled during growth and morphogenesis under the influence of morphogens and mechanical tension (MT). E-Cadherin – the primary cell-cell adhesion protein plays a crucial role in maintaining integrity and dynamic remodelling of epithelial tissues. But how MT, a key regulator of epithelial dynamics, influences the turnover of E-Cadherin is unknown. Here, we use in vivo model system of Drosophila pupal wing, a relatively flat tissue that generates MT during morphogenesis. Using cortical laser ablation and Fluorescence recovery after photobleaching (FRAP) techniques, we show that E-Cadherin turnover is strongly dependent on MT. By reducing tension in the pupal wing either by genetic perturbation or laser ablation we revealed that MT regulates E-Cadherin turnover. We show that mechano-regulation of E-Cadherin was mediated by modulation of endocytosis. Upon knocking down p120ctn, this mechano-regulation was abolished. Based on our findings, we propose that p120ctn is a novel mechanotransducer that modulates endocytosis of E-Cadherin by MT. Our results open new avenues towards understanding the role of p120ctn and E-Cadherin turnover in the link between tumour metastasis and its mechanical environment.