Homeostatic Regulatory Circuits of the Mammalian Cell: Focus on the Biosynthetic Membrane Transport Apparatus

Cellular functions are controlled by an extensive regulatory network, within which one can distinguish two principal classes of circuits. One is involved in cellular responses to extracellular cues via membrane receptors facing the extracellular space, while the other consists of internal sensors, controllers and effectors that operate to maintain homeostasis, coordinate different cellular functions, and optimize its overall system’s performance. The former class of receptor signaling circuit has been investigated over the last decades in the context of many cell functions and it is well understood, while the latter has been studied much less extensively, or by comparison, neglected, at least in many areas, despite its fundamental importance in physiology and pathology. This article focuses mainly on the second class of circuits, and, in particular, on the internal control mechanisms operating in the biosynthetic membrane transport (BMT) apparatus, a fundamental cell module with a major role in the cellular organization. The BMT apparatus is responsible for the synthesis, folding, processing and delivery to their final cellular destinations of a third of the eukaryotic proteome. Through these functions, the transport apparatus maintains the correct morphology, composition and function of most cellular organelles by influencing the cell–cell and cell–environment communications. Moreover, the BMT interacts with other cellular modules like energy metabolism and autophagy in the execution of complex programs initiated by surface receptors, such as cell growth, migration and differentiation. We analyze the molecular composition, design principles, coordination with other modules, and significance in physiology and pathology of the control systems operating in the BMT.