Protein Receptor Opens the Gated Pores

Dentistry Today

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If you are among the millions who go to the movies, chances are you’ve spent a few minutes waiting for patrons from the earlier show to exit the theater. Theaters must move ‘em out before they can pack ‘em back in. This same concept of efflux and influx holds true for calcium-signaling cells in the body. They must first expel their internal stores of calcium before allowing an influx of new calcium ions. This biochemical process, com­mon in myriad physiological processes from muscle contraction to saliva secretion, is initiated through a protein receptor that activates the opening and/or closing of a gated pore in the cell outer membrane. This type of pore is called a store-operated calcium channel (SOC). Scientists have identified 2 major varieties of SOCs on the plasma membrane, the cell’s envelope: the TRPC and the Orai channels. Interestingly, both are gated by the same calcium sensor, STIM1, that resides in the endoplasmic reticulum, where the molecular information grows thin. Researchers would like to know exactly how STIM1 gates the 2 channels and whether the protein does so in exactly the same way. In Molecular Cell (November 7, 2008), National Institute of Dental and Craniofacial Research (NIDCR) grantees and colleagues found that STIM1 gates TRPC channels through an electrostatic inter­action. In this case, a positively charged region of STIM1 specifically interacts in a lock-and-key manner with 2 negatively charged and highly conserved aspartate residues of the TRPC channel. How­ever, in the Orai channels, STIM1 relies on a different and still un­deter­mined mechanism. The discovery of the electrostatic gating mechanism provides a novel and invaluable lead to understand the operation of the TRPC channel. Clearing the way for additional research to fine tune calcium signaling at the cellular level which can possibly improve salivary flow.


(Source: NIDCR, Science News in Brief, January 5, 2009)