Membrane Mechanics at the Endoplasmic Reticulum

Mechanosensation and morphosensation relate to the responsiveness of cellular signal transduction events to mechanical or geometrical cues, respectively. On one hand, integrin activation and focal adhesion formation at the plasma membrane are well-characterized examples of how mechanical perturbations can affect protein conformation and downstream signaling. On the other hand, curvature sensing proteins are a good example of morphosensors, since their membrane binding affinity is dependent on a geometrical cue (in this case, membrane curvature). In the process of membrane fission, the size of the transport carriers –and therefore the timing of the fission event– normally responds to the structure of the proteins curving the membrane. However, in some special cases, the size of the transport carriers needs to be readjusted to commensurate with the size of the proteins therein contained.

To study this fascinating process, we are focusing on how the ER budding machinery is modulated to generate transport carriers commensurate with the size of large cargos, such as collagens, a process dependent on a protein named TANGO1. We combine molecular cell biology and biochemistry, super-resolution nanoscopy, and quantitative physical modeling, and found that TANGO1, by assembling into a ring at ER exit sites, generates a semistable sub-domain across two compartments. The processes that allow this assembly also coordinately select, partition, and organize folded cargo, export machinery, and membrane acquisition for the generation of a transport carrier commensurate with the size of large cargos, such as collagens.