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When the calcium store is empty! How does STIM1 become the calcium-sensing hero in the cell?
In the microscopic world of life, calcium ions (Ca2+) are important signaling molecules inside cells, affecting a variety of physiological processes. When these calcium stores are empty, how do cells respond? With the deepening of the understanding of calcium channels, the protein STIM1 is gradually recognized as a key player in the regulation of calcium ions. Through its synergistic interaction between the endoplasmic reticulum and the cell membrane, STIM1 becomes a true calcium-sensing hero.
The role of CRAC channel and STIM1
Calcium release-activated channels (CRAC) are a group of specialized calcium channels that are responsible for replenishing calcium from outside the cell when intracellular calcium stores are depleted. The core protein of the CRAC channel is Orai, and STIM1 is its necessary accessory. STIM1 is located on the endoplasmic reticulum membrane and can sense the concentration of internal calcium ions. Once it finds that the calcium ion concentration is too low, it will quickly change its shape and interact with Orai on the cell membrane surface to open calcium channels.
The binding of STIM1 to Orai initiates a process that not only reintroduces calcium ions into the cell but also promotes the activation of a series of signaling pathways.
Structure and function of STIM1
STIM1 is a transmembrane protein with a relatively simple structure of approximately 250 amino acid residues that can efficiently perform its calcium sensing function. When the calcium concentration in the ER decreases, STIM1 molecules will accumulate on the cell membrane, prompting the opening of CRAC channels, thereby promoting the entry of calcium ions.
The role of STIM1 in lymphocytes
In the immune system, lymphocytes have a particularly urgent need for calcium. STIM1 was found to be expressed four times more in T cells than in B cells in mice, allowing the T cells to cope with more calcium influx. This function is crucial in immune responses, such as promoting the activation of the transcription factor NFAT, thereby affecting gene expression.
The CRAC channel in lymphocytes is not only the entry channel for calcium, but also the "hearing" of the cell's response to the external environment, which can regulate multiple physiological processes such as cell proliferation and development.
Recombination and Regulation: Regulation of SOCE
Storage-operated calcium entry (SOCE) is an important mechanism for regulating intracellular calcium balance. STIM1 and Orai are core components of this mechanism. In particular, SARAF, a negative regulator, helps cells self-regulate in the presence of calcium overload by interacting with STIM1 to prevent cells from being damaged by excess calcium.
The role of SARAF is particularly important in maintaining appropriate intracellular calcium concentrations and avoiding calcium-induced toxicity.
The association between STIM1 and genetic diseases
In some patients with severe combined immunodeficiency (SCID), defects in STIM1 or Orai lead to a failure of the CRAC channel, which prevents their immune systems from properly fighting foreign pathogens. Research on this type of disease not only helps to understand the basis of immune function, but may also guide future treatment options.
Conclusion
STIM1, with its unique structure and function, plays an indispensable role in the opening and regulation of calcium channels. STIM1 functions in everything from cell survival to immune responses. With the development of biomedicine, how will we use these discoveries to improve human health in the future?
