Control Systems of Membrane Transport at the Interface between the Endoplasmic Reticulum and the Golgi

A fundamental property of cellular processes is to maintain homeostasis despite varying internal and external conditions. Within the membrane transport apparatus, variations in membrane fluxes from the endoplasmic reticulum (ER) to the Golgi complex are balanced by opposite fluxes from the Golgi to the ER to maintain homeostasis between the two organelles. Here we describe a molecular device that balances transport fluxes by integrating transduction cascades with the transport machinery. Specifically, ER-to-Golgi transport activates the KDEL receptor at the Golgi, which triggers a cascade that involves Gs and adenylyl cyclase and phosphodiesterase isoforms and then PKA activation and results in the phosphorylation of transport machinery proteins. This induces retrograde traffic to the ER and balances transport fluxes between the ER and Golgi. Moreover, the KDEL receptor activates CREB1 and other transcription factors that upregulate transport-related genes. Thus, a Golgi-based control system maintains transport homeostasis through both signaling and transcriptional networks. [Display omitted] •A Golgi-based homeostatic system senses and responds to incoming transport fluxes•Transport to the Golgi activates the KDEL receptor and a Gs-PKA signaling cascade•The KDELR Gs-PKA signaling cascade regulates retrograde transport machinery•KDELR signaling upregulates transcription of traffic machinery proteins Cancino et al. provide insight into the regulation of membrane flux balance between the endoplasmic reticulum and the Golgi. They show that a Golgi-based control system involving the KDEL receptor integrates signal transduction cascades with the transport machinery and transcriptional networks to maintain transport homeostasis between the two organelles.