Phase separation of equilibrium polymers of proteins in living cells

Abstract

A number of proteins polymerise reversibly in living cells. The equilibrium polymers are functional: if mutant proteins are made that cannot polymerise, then these proteins cannot perform their biological functions. Furthermore, these polymers of proteins appear to phase separate inside the cell. The dynamics of one of these polymerising, phase separating proteins has been studied viafluorescence recovery after photobleaching (FRAP) by Bienz and coworkers. Here, their data is compared with the results of quantitative modelling to gain a better understanding of the dynamics of this protein inside a cell. The protein is called Dishevelled; it is a protein essential to the development of all animals and the name originates in the disruption of hair formation in a mutant version of this protein. It is not known how polymerisation and phase separation enable Dishevelled to perform its biological function but here we propose and discuss two possibilities. The first is that the cell is exploiting the inherently sharp, switch-like nature of a phase transition to respond in a switch-like way to a external signal. The second is that phase separation dynamically creates a compartment (the more concentrated phase) into which other proteins partition.