Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Fameli, N; van, Breemen, C; Groschner, K.
Nanojunctions: Specificity of Ca2+ signaling requires nano-scale architecture of intracellular membrane contact sites.
Cell Calcium. 2024; 117: 102837
Doi: 10.1016/j.ceca.2023.102837
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Fameli Nicola
- Groschner Klaus
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- Abstract:
- Spatio-temporal definition of Ca2+ signals involves the assembly of signaling complexes within the nano-architecture of contact sites between the sarco/endoplasmic reticulum (SR/ER) and the plasma membrane (PM). While the requirement of precise spatial assembly and positioning of the junctional signaling elements is well documented, the role of the nano-scale membrane architecture itself, as an ion-reflecting confinement of the signalling unit, remains as yet elusive. Utilizing the Na+/Ca2+ Exchanger-1 / SR/ER Ca2+ ATPase-2-mediated ER Ca2+ refilling process as a junctional signalling paradigm, we provide here the first evidence for an indispensable cellular function of the junctional membrane architecture. Our stochastic modeling approach demonstrates that junctional ER Ca2+ refilling operates exclusively at nano-scale membrane spacing, with a strong inverse relationship between junctional width and signaling efficiency. Our model predicts a breakdown of junctional Ca2+ signaling with loss of reflecting membrane confinement. In addition we consider interactions between Ca2+ and the phospholipid membrane surface, which may support interfacial Ca2+ transport and promote receptor targeting. Alterations in the molecular and nano-scale membrane organization at organelle-PM contacts are suggested as a new concept in pathophysiology.
- Find related publications in this database (Keywords)
- Calcium signalling
- PM-ER junctions
- Nanojunctions
- Na+/Ca2+exchanger
- Stochastic model
- Computational simulation