Abstract
Nano-junctions between the endoplasmic reticulum and cytoplasmic surfaces of the plasma membrane and other organelles shape the spatiotemporal features of biological Ca2+ signals. Herein, we propose that 2D Ca2+ exchange diffusion on the negatively charged phospholipid surface lining nano-junctions participates in guiding Ca2+ from its source (channel or carrier) to its target (transport protein or enzyme). Evidence provided by in vitro Ca2+ flux experiments using an artificial phospholipid membrane is presented in support of the above proposed concept, and results from stochastic simulations of Ca2+ trajectories within nano-junctions are discussed in order to substantiate its possible requirements. Finally, we analyze recent literature on Ca2+ lipid interactions, which suggests that 2D interfacial Ca2+ diffusion may represent an important mechanism of signal transduction in biological systems characterized by high phospholipid surface to aqueous volume ratios.
Highlights
The discovery of ATP-driven accumulation of ionic calcium (Ca2+) by isolated vesicles of the endoplasmic reticulum (ER) of skeletal muscle in 1962 [1] established its fundamental role in cellular Ca2+ signaling
Once Ca2+ transported from the cis-side of the flux chamber has been chelated by EDTA, which is dissolved in a large volume of buffered solution on the transside, it cannot rebind to the PL membrane, but is replaced by the Ca2+arriving from the cis-side
Returning to the example of NCX-mediated sarcoplasmic reticulum (SR) refilling in vascular smooth muscle, we propose that Ca2+ enters the NJ via the reverse mode of NCX located in the junctional domain of the plasma membrane (PM)
Summary
The discovery of ATP-driven accumulation of ionic calcium (Ca2+) by isolated vesicles of the endoplasmic reticulum (ER) of skeletal muscle in 1962 [1] established its fundamental role in cellular Ca2+ signaling. Known Ca2+-sensitive functions include the following: contraction; relaxation; hyperpolarization; depolarization; ER refilling; ER unloading; secretion; endocytosis; protein folding; apoptosis; mitochondrial energetics; neurotransmitter release; intracellular trafficking; and intercellular communication via gap junctions. For this single ionic messenger to harmoniously control such a great range of biological mechanisms, it is crucial that its signals are delivered with pinpoint precision and millisecond timing. We propose that, in addition to the three NJ-related mechanisms mentioned above, a fourth requirement consists of 2D exchange diffusion of Ca2+ on the targeted phospholipid membrane surface
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