Measuring the effects of α1 -antitrypsin polymerisation on the structure and biophysical properties of the endoplasmic reticulum.

An important function of the endoplasmic reticulum (ER) is to serve as a site of secretory protein folding. When the accumulation of misfolded proteins threatens to disturb luminal homoeostasis, the cell is said to experience ER stress. By contrast, the accumulation of well-folded proteins inside the ER leads to a distinct form of strain called ER overload. The serpins comprise a large family of proteins whose folding has been studied in great detail. Some mutant serpins misfold to cause ER stress, whereas others fold but then polymerise to cause ER overload. We discuss recent advances in the use of dynamic fluorescence imaging to study these phenomena. We also discuss a new technique that we recently published, rotor-based organelle viscosity imaging (ROVI), which promises to shed more light on the biophysical features of ER stress and ER overload.