Signaling pathways between the plasma membrane and endoplasmic reticulum calcium stores

Abstract.

This review discusses multiple ways in which the endoplasmic reticulum participates in and is influenced by signal transduction pathways. The endoplasmic reticulum provides a Ca²⁺ store that can be mobilized either by calcium-induced calcium release or by the diffusible messenger inositol 1,4,5-trisphosphate. Depletion of endoplasmic reticulum Ca²⁺ stores provides a signal that activates surface membrane Ca²⁺ channels, a process known as capacitative calcium entry. Depletion of endoplasmic reticulum stores can also signal long-term cellular responses such as gene expression and programmed cell death or apoptosis. In addition to serving as a source of cellular signals, the endoplasmic reticulum is also functionally and structurally modified by the Ca²⁺ and protein kinase C pathways. Elevated cytoplasmic Ca²⁺ causes a rearrangement and fragmentation of endoplasmic reticulum membranes. Protein kinase C activation reduces the storage capacity of the endoplasmic reticulum Ca²⁺ pool. In some cell types, protein kinase C inhibits capacitative calcium entry. Protein kinase C activation also protects the endoplasmic reticulum from the structural effects of high cytoplasmic Ca²⁺. The emerging view is one of a complex network of pathways through which the endoplasmic reticulum and the Ca²⁺ and protein kinase C signaling pathways interact at various levels regulating cellular structure and function.