Frédéric Pincet, laureate of the 2020 ERC Synergy call

Frédéric Pincet, Senior CNRS scientist in the Membrane Molecular Mechanisms team at LPENS, is laureate of the 2020 ERC Synergy call.
He will test the hyposhesis that the protein secretory pathway is built in 3 dimensions by the self-organization of 2D-liquid crystal domains of membrane proteins.

Fully one third of the proteins encoded in the human genome are sorted from each other during their transport through a series of attached membrane-enclosed compartments called the ER/Golgi system. How can ER/ Golgi system have steady‐state polarity while most of their components are so fluidly interchanging? How can this system be so dramatically elastic, and like a stretched spring always return to its original state? This has been an unsolved puzzle since the first description of the ER/Golgi system 50 years ago.

The recent discovery that some proteins self-organize into liquid-like droplets casts these old facts in a new light. The simplest explanation would be that the ER/Golgi system is fundamentally a liquid with a phase‐separated internal organization. Analogous liquid like condensates or phases attached to membrane surfaces would form essentially 2 dimensional self-organized compartments, resembling “liquid crystals”. The surfaces of the ER/Golgi compartments are coated with an abundant family of proteins called Golgins, and each layer has its own set of Golgins. We discovered that these Golgins self-assemble into liquid-like arrangements both in the test tube and in cells. We therefore hypothesize that the intrinsic physical properties of Golgins dictate the organization and precise ordering of membrane compartments in the ER/Golgi system.

In our novel hypothesis, analogous to the phase separation of oil from water, Golgins spontaneously separate into 2 dimensional liquid crystal-like phases based on their mutual attraction or repulsion in cis. Whereas, adhesion between these 2 dimensional phases in trans is used to build and layer a polarized 3 dime