Abstract

Introduction: Organelle interplay adds another level of complexity requiring intense analysis to fully understand the cell functioning Inter-organelle signaling plays important roles in cell physiology ranging from cell metabolism, signaling to spatial and temporal adaptation to external and internal perturbations. Nevertheless, how such perturbations orchestrate a coordinated response on specific organelles, and how organelles function influences each other has not been considered or demonstrated in detail. During protein secretion cargo is transported through a series of compartments to reach their destination which are regulated by a Golgi-based control system. Surprisingly we have found that during secretion, Golgi-complex signaling regulate lysosomal dynamics and positioning. Blocking lysosome repositioning revealed an unpredicted and unreported function of lysosomes and autophagy as positive regulators of protein secretion from Golgi-complex. Here we show how coordinated inter-organelle crosstalk results to be crucial to engage functional cellular modules such as microtubule cytoskeleton molecular motors, transport and the nutrient sensing machinery which mutually regulate their function to keep cell homeostasis. Material and Methods: Human cells, cell microinjection, quantitative fluorescence image, shRNA, Results: ER to Golgi transport activates KDELR which in turn increases the number of lysosome-related organelles at the perinuclear area; lysosomal relocation is driven by Dyn-LRB1 phosphorylation at S73 by KDELR-dependent activation of PKA. Inhibition of lysosome relocation and/or autophagy impairs cargo secretion from Golgi to plasma membrane.