Abstract
Organisms rely on correctly folded proteins to carry out essential functions. Protein quality control factors guard proteostasis and prevent protein misfolding. When quality control fails and in response to diverse stresses, many proteins start to accumulate at specific deposit sites that maintain cellular organization and protect the functionality of coalescing proteins. These transitions involve dedicated proteins that promote coalescence and are facilitated by endo-membranes and cytoskeletal platforms. Moreover, several proteins make use of weak multivalent interactions or conformational templating to drive the formation of large-scale assemblies. Formation of such assemblies is often associated with a change in biochemical activity that can be used by cells to execute biochemical decisions in a localized manner during development and adaption. Since all assembly types impact cell physiology, their localization and dynamics need to be tightly regulated. Interestingly, at least some of the regulatory mechanisms are shared by functional membrane-less organelles and assemblies of terminally aggregated proteins. Furthermore, constituents of functional assemblies can aggregate and become non-functional during aging. Here we present the current knowledge as to how coalescing protein assemblies are spatially organized in cells and we postulate that failures in their spatial confinement might underscore certain aspects of aging and neurodegenerative diseases.