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SHR Neuro Cancer Cardio Lipid Metab 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
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Leading authors 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

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