Tissue Specificity: The Role of Organellar Membrane Nanojunctions in Smooth Muscle Ca(2+) Signaling

Nicola Fameli, A Mark Evans, Cornelis van Breemen

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)peer-review

Abstract / Description of output

In this chapter we examine the importance of cytoplasmic nanojunctions-nanometer scale appositions between organellar membranes including the molecular transporters therein-to the cell signaling machinery, with specific reference to Ca(2+) transport and signaling in vascular smooth muscle and endothelial cells. More specifically, we will consider the extent to which quantitative modeling may aid in the development of our understanding of these processes. Testament to the requirement for such approaches lies in the fact that recent studies have provided evermore convincing evidence in support of the view that cytoplasmic nanospaces may be as significant to the process of Ca(2+) signaling as the Ca(2+) transporters, release channels, and Ca(2+)-storing organelles themselves. Moreover, the disruption and/or dysfunction of cytoplasmic nanospaces may be central to the origin of certain diseases. By way of introduction, we provide a historical perspective on the identification of smooth muscle cell plasma membrane (PM)-sarcoplasmic reticulum (SR) nanospaces and the early evidence in support of their role in the generation of asynchronous Ca(2+) waves. We then summarize how stochastic modeling approaches can aid and guide the development of our understanding of two basic functional steps leading to healthy smooth muscle cell contraction. We furthermore outline how more sophisticated and realistic quantitative stochastic modeling may be employed not only to test working hypotheses, but also to lead in their development in a manner that informs further experimental investigation. Finally, we consider more recently defined nanospaces such as the lysosome-SR junction, by way of demonstrating the importance of quantitative stochastic modeling to our understanding of signaling mechanisms.

Original languageEnglish
Title of host publicationStore-Operated Ca²⁺ Entry (SOCE) Pathways
Number of pages22
Publication statusE-pub ahead of print - 13 Sept 2017

Publication series

Name Advances in Experimental Medicine and Biology

Keywords / Materials (for Non-textual outputs)

  • Journal Article


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