Virtually all functions of a cell are influenced by cytoplasmic [Ca 2+] increases. Inositol 1,4,5-trisphosphate receptor (IP 3R) channels, located in the endoplasmic reticulum (ER), release Ca2+ in response to binding of the second messenger, IP3. IP3Rs thus are part of the information chain interpreting external signals and transforming them into cytoplasmic Ca2+ transients. IP3Rs function as tetramers, each unit comprising an N-terminal ligand-binding domain (LBD) and a C-terminal channel domain linked by a long regulatory region. It is not yet understood how the binding of IP3 to the LBD regulates the gating properties of the channel. Here, we use the expression of IP3 binding protein domains tethered to the surface of the endoplasmic reticulum (ER) to show that the all-helical domain of the IP3R LBD is capable of depleting the ER Ca2+ pools by opening the endogenous IP3Rs, even without IP3 binding. This effect requires the domain to be within 50 Å of the ER membrane and is impaired by the presence of the N-terminal inhibitory segment on the LBD. These findings raise the possibility that the helical domain of the LBD functions as an effector module possibly interacting with the channel domain, thereby being part of the gating mechanisms by which the IP3-induced conformational change within the LBD regulates Ca2+ release.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - May 31 2005|
- Ca channel
- Endoplasmic reticulum
- Red fluorescent protein
ASJC Scopus subject areas