Mechanotransduction at the Golgi apparatus: a role for CDC42? – MECHANGOLGI

Cells can sense and respond to external forces and mechanotransduction events appear to be critical for most cellular functions. While mechanotransduction has been extensively studied at the plasma membrane and at the nucleus, the effect of forces on other intracellular organelles is still not clear. Our project will study mechanotransduction at the Golgi apparatus, a central organelle for intracellular transport pathways. We will focus on the role of the small G protein CDC42, a Golgi-localized protein involved in polarized membrane trafficking, which has recently been suggested to be involved in mechanosensing in the secretory pathway. We have three objectives: 1) quantifying the impact of external constraints on Golgi mechanics and tension; 2) measuring the effects of CDC42 activity on force transduction at the Golgi apparatus; and 3) investigating the role of CDC42 in the mechanosensitivity of the secretory pathway. To achieve these objectives, we will use a combination of biophysics and cell biology approaches. A range of mechanical cues will be applied for instance by intracellular optical tweezers, by osmotic shocks, or by plating cells on substrates of defined rigidities. In parallel, Golgi tension will be monitored with recently developed biosensors. The role of CDC42 in mechanotransduction at the Golgi apparatus will be investigated by modulating CDC42 expression and activity. Conversely, we will study the putative effects of mechanical constraints on CDC42 activity and Golgi tension. We hope to better decipher how the Golgi apparatus can act as a tension sensor and regulate, via CDC42, the mechanosensitivity of post-Golgi trafficking.