Quality Control and Fidelity

Abstract

Like factories in miniature, cells must organize complex arrays of machinery into robust and accurate processes. It comes as no surprise, then, that diverse quality control and precision mechanisms underlie virtually all aspects of cellular function. In this issue, we are pleased to present a group of Review articles exploring facets of key cellular infrastructure and the consequences of their failure. These Reviews focus on four particular areas of rapidly advancing research relating to cytoskeleton-based structures, organellar membranes, protein biosynthesis, and chromosome integrity.Our Review Feature begins with a discussion of cytoskeleton-based structures, focusing on those built from microtubules, from Radhika Subramanian and Tarun Kapoor. Beyond their obvious structural roles, dynamic assemblies of microtubules are also central to diverse cellular processes such as chromosome segregation, organelle positioning, and cilium formation. How do regulatory inputs ensure the essential qualities, like shape and size, of these architectures? Subramanian and Kapoor argue that basic recurring structural motifs in cytoskeletal arrays provide points of regulation and promote self-organized assembly of diverse architectures.Copyright iStockphoto/RomanOkopnyView Large Image | View Hi-Res Image | Download PowerPoint SlideAkin to the precision necessary to build specific cellular structures, the membrane surfaces of organelles such as the ER and Golgi must also provide precisely defined domains to facilitate a multitude of specific protein interactions important to signal transduction, vesicular trafficking, and lipid metabolism. Joelle Bigay and Bruno Antonny provide a conceptual framework for understanding how changes in the deceptively simple physical parameters of membrane curvature, lipid packing, and electrostatics provide the necessary inputs that generate specificity in protein-membrane interactions.Of course, precision mechanisms are far from being fail-safe in the maintenance of fidelity. Thus, there exist additional layers of quality control dedicated to recognizing when these mechanisms have failed and providing damage control. No different from an assembly line in a factory, the assessment and removal of defective products at multiple stages throughout the manufacturing process provides added degrees of fidelity. Monica Rodrigo-Brenni and Ramanujan Hegde explore this idea of additive quality-control systems and the coupling of synthesis and degradation in the context of protein biosynthesis. Not only do sequential checkpoints survey the nascent polypeptide throughout its maturation, but the protein biosynthetic machinery is also increasingly found to associate with protein degradation factors.Unlike protein biosynthesis, in which degradation of defective products is the dominant mode of quality control, safeguarding the integrity of the genome must rely instead on repair. Not surprisingly, failure of these error-correction mechanisms has catastrophic consequences not only for chromosome integrity but also for cellular and organismal health. Focusing on the recently discovered phenomenon of chromothripsis, the complex and extensive gross chromosomal rearrangements observed in certain cancer cells, Mathew Jones and Prasad Jallepalli review the processes that regulate chromosome integrity and delve into the ramifications of their dysfunction.We hope you will enjoy reading these Reviews and considering the diverse range of cellular strategies for quality control and fidelity that they present.On behalf of the Developmental Cell editorial team.