Calcium signaling: STIM revisited

In cell signaling, calcium is king. The flux of calcium ions across cell membranes regulates cellular activities from muscle contraction to neuron firing to immune cell function.

By | January 15, 2008

In cell signaling, calcium is king. The flux of calcium ions across cell membranes regulates cellular activities from muscle contraction to neuron firing to immune cell function. A talk I saw here at the Keystone symposium on the molecular basis for biological membrane organization in Big Sky, Montana, presented some significant steps forward in understanding the molecular pathway whereby the cell senses the depletion of calcium from stores in the endoplasmic reticulum and in order to allow the influx of fresh supplies. Jen Liou, a Stanford biologist who I interviewed for a linkurl:story; last year about her discovery of the key signaling protein involved in store-operated calcium entry (SOC), presented new data on the pathway and told me that she plans to continue focusing on it as she seeks to set up her own lab. Researchers still don't know how exactly the protein, called STIM1, interacts with and opens the calcium channel protein, Orai1, but Liou's presentation focused on her continued work on the functional dynamics of STIM proteins. She said that STIM1, which was though to be the main player in SOC, not only translocates from the endoplasmic reticulum to areas near the plasma membrane, but also oligomerizes prior to this translocation. Liou has found that this oligomerization may be key to STIM1's interaction with Orai1 or some unknown intermediate between the two proteins. Observing this phenomenon meant that Liou could identify a C-terminal amino acid motif that was likely binding STIM1 to phospholipids in the plasma membrane. Liou also presented data that suggests a functional role for STIM2, a protein closely related to STIM1. She said STIM2 may be maintaining a stable calcium gradient prior to the dramatic influx mediated by STIM1. As we chatted in front of her poster last night, I asked Liou how all the other potential players, such as the cell's cytoskeleton and lipids, might be affecting the dance between STIM1 and Orai1. She admitted that these aspects of the process are not yet well understood and that screening remains to be done to uncover other molecular players that may be functioning in SOC. "There is much more work to be done," Liou said, and she's planning on doing it. She's looking to set up her own lab (currently she works under linkurl:Tobias Meyer; at Stanford), which she will devote to elucidating the molecular intricacies of SOC.


Avatar of: Sergio Stagnaro

Sergio Stagnaro

Posts: 59

January 17, 2008

Editors,\nas regards signaling cascades to record receptor activation, all around the world, authors seem unfortunately to know only the contact stimulation of receptors, based on the information transmission in local realm, according to deterministic mechanics, characterized by Space/Time Matrix with 4 Dimensions (3 DS and 1DT), wherein Time is linear and reversible. If we admit that in biological systems there is only local realm, in which information transmission needs energy and time, than we aren?t able to comprehend neither the real mechanisms of the very numerous biophysical semeiotics reflexes, nor the simultaneity they are based on (1). For instance, digital pressure applied upon skin projection area of SST-RH neuronal diencephalic centre, brings about simultaneously local type I, associated, microcirculatory activation ( and pancreas size increasing (1-5), showing the later a characteristic behaviour in health, rather different from that of individual involved by diabetic constitution, diabetic inherited real risk, and obviously by diabetes (5).\nIn fact, Paolo Manzelli and I have recently demonstrated at the bedside for the first time that in all biological systems, besides local realm, really exist also non-local realm, wherein energy information is simultaneous and doesn?t need energy for working (3-5). Exclusively such as new knowledge highlights biophysical-semeiotics reflex mechanisms. Finally, when physicians all around the world will learn and apply these new knowledges, which justify the term Biophysical-Quantistic-Semeioticics, my renowed friend and co-worker Paolo Manzelli suggested, both diagnosis and therapeutic monitoring will change in a paramount manner(6). \n\n\n\n1. Stagnaro-Neri M., Stagnaro S. (2004). Introduction to Biophysical Semeiotica. Oncological Terrain (translated from italian). Eds.Travel Factory, Roma. \n2. Stagnaro Sergio e Paolo Manzelli. (2007), Biophysical semeiotica: non-local Realm in Biology (translated from italian).,\n3. Stagnaro Sergio e Paolo Manzelli. (2007) Endocrinological Biophysical: Quantum Mechanics and Hormone Action Mechanism. (translated from italian).,\n4. Stagnaro Sergio e Paolo Manzelli. (2008), Limits of official Medicine. Lory?s Experiment. (translated from italian). \n 5. Stagnaro Sergio. (2007) Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology.\n6. Stagnaro Sergio Semeiotica Biofisica Quantistica. Diagnosi precoce e rapida di Metastasi Ossee.,

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