The endoplasmic reticulum as a transport and delivery network for calcium ions.

The endoplasmic reticulum serves as an interconnected network of tunnels for the distribution and sorting of proteins, lipids, and ions throughout a cell. The structure of the network can be perturbed by a variety of morphogen mutations and drug treatments, and defects in the proteins responsible for ER shaping are associated with some human neurodegenerative diseases. Using a combination of mathematical modeling, numerical simulations, and experimental measurements we explore how the architecture of the ER modulates transport within it. In particular, we focus on the role of intra-luminal transport of buffer proteins and calcium ions in determining the rate and magnitude of local calcium release events from the ER. We show that mobile buffers of moderate binding strength and a well-connected network are predicted to enhance local calcium release. Using genetic perturbation of ER morphogens that lead to fragmentation or increased tubule length in the ER we demonstrate that these morphological changes indeed lead to reduced magnitude in observed localized calcium puffs. Our work highlights the importance of ER morphology in controlling its structure as an intracellular transport hub.