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Scripps Research scientists show how shifts in temperature prime immune response
Date:5/6/2011

associate in the Patapoutian laboratory. "The temperature drops significantly when, say, immune cells move from the 37 degree Celsius temperature of the spleen to skin, where it is normally 33 degrees. During fever, core body temperature can rise to 41 degrees." Scientists have discussed for decades whether fever is beneficial to the immune system. The researchers believe that identification of a molecular sensor of temperature within immune cells provides a novel avenue to address such questions mechanistically.

The research team, which included Bertrand Coste and Jayanti Mathur, also of the Patapoutian lab, found that STIM1 can be activated by heat with a high degree of temperature sensitivity. Both STIM1 and a plasma membrane pore-forming protein known as Orai1 have recently been identified as essential components of the so-called the calcium release activated calcium (CRAC) channel. But STIM1 had not been known to be heat sensitive until this research, according to Xiao.

The process goes like this: STIM1 proteins are located on the ER, which is the organelle that stores calcium inside the cell. When a sudden change in temperature occurs, STIM1 proteins cluster together and translocate close to the plasma membrane. There, these clusters then can activate Orai1, which leads to the opening of the channel pore and an influx of calcium to activate the cell. Calcium is essential for a number of cellular functions, and, in immune cells, a sustained influx of calcium into these cells activates gene expression and cell proliferation. It turns the immune cell "on," Xiao said.

The function of STIM1 and Orai1 had already been known to be critical to immune function, Xiao said. Mutations in genes encoding either of the proteins lead to development of severe combined immunodeficiency (SCID), the so-called "bubble boy" disease characterized by a complete absence of immunity.

Given the relatively wide expression pattern of STIM1, the researc
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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