Chaperones and multitasking proteins in the nucleolus

Abstract

A large number of molecular chaperones and multitasking proteins are located in the nucleolus. The nucleolar association of many of these proteins is dynamic and regulated by the physiological state of the cell. Recent progress in proteomics, imaging and image quantification advanced our understanding of the nucleolar response to stress and disease. In particular, heat shock proteins and their co-chaperones in conjunction with nucleolar multitasking proteins are components that are critical for the proper organization and function of nucleoli, especially under stress and disease conditions. To accomplish these tasks, chaperones together with multitasking proteins are likely to build a compartment-specific network in the nucleolus, where it supports protein homeostasis. However, despite the importance of chaperones and co-chaperones for cellular proteostasis, little is known about their specific functions in the nucleolus. Here, we focus on the targeting signals and molecular mechanisms that underlie the nucleolar trafficking of chaperones and multitasking proteins, as exemplified by heat shock protein hsc70 and the nucleolar proteins B23, nucleolin and Nopp140. It will be discussed how their subcellular localization is affected by physiological or environmental changes and modulated by cell signaling. We describe several links that connect chaperones with nucleolar multitasking proteins and speculate on the specific contributions of chaperones to nucleolar biology. The chapter concludes by highlighting some of the open questions as they are emerging from the current developments in the field.