Mechanisms regulating STIM expression and function in Ca2+ signaling

Published on February 6, 2013 Reviewed on August 12, 2020   34 min

Other Talks in the Category: Biochemistry

0:00
Hello my name is Jonathan Soboloff and today I'm going to talk a little bit about some recent work performed in my lab, investigating mechanisms regulating STIM expression and function in calcium signaling.
0:14
Before getting too far into my current research, I'd like to talk a little about the physiological roles of calcium signals. Calcium signals control a wide variety of distinct physiological events. Whereas calcium signals themselves typically occur quite rapidly in a time frame of seconds to minutes, the physiological consequences of these signals can last over a much longer time period. Some of the immediate effects of calcium signals can be detected immediately over a time frame, similar to the calcium signal itself. For example, muscle contraction, changes in the metabolic state of certain enzymes, or membrane fusion, such as for example in secretion. Other calcium signals occur over a much longer time frame, really long after the calcium signal has already ended, such as changes in gene expression, changes in cell proliferation, or changes in apoptosis (otherwise known as cell death). The major goal of my lab is to understand this link between short-term changes in calcium signals and these longer-term changes in cell function.
1:20
Now I'd like to talk a little about receptor-mediated control of calcium signals. At rest, the concentration of calcium in the cytosol is many-fold lower than outside of the cell or in the lumen of the. This difference is maintained by the combined action of the plasma membrane calcium ATPase (PMCA) and the sarco/endoplasmic reticulum calcium ATPase (SERCA). When a ligand binds to a PLC (phospholipase C-coupled receptor), it initiates a series of events leading to elevation of cytosol calcium concentration. The first step in this process is breakdown of phosphatidyl inositol (PIP2) into two bio-active metabolites, diacylglycerol (DAG) and IP3. DAG has a number of different targets, one of which is receptor-operated calcium channels (ROCs), which upon binding of diacylglycerol permit the entry of calcium into the cytosol from the extracellular space. IP3 binds to its receptor on the Membrane, causing the movement of calcium out of the Lumen and into the cytoplasm, and this movement of calcium out of the Lumen tends to cause a depletion of Calcium concentration. This Calcium depletion leads to the activation of a separate class of calcium channels, termed store-operated calcium channels (SOCs). Because both SOCs and ROCs are activated downstream of receptors at least physiologically, there's been a great deal of confusion over the years over whether a channel is receptor-operated or store-operated. Much of this confusion was addressed in 2005 and 2006, with the identification of the molecular mediators of SOC and it's these proteins that have been the focus of my research since that time.
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Mechanisms regulating STIM expression and function in Ca2+ signaling

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