Regulation of Inositol 1,4,5-Trisphosphate Receptors by Phosphorylation and Adenine Nucleotides

Isoform- and Species-specific Control of Inositol 1,4,5-Trisphosphate (IP3) Receptors by Reactive Oxygen Species

“…Ca 2ϩ release from IP 3 Rs localized in the vicinity of mitochondria also plays a pivotal role in propagation of Ca 2ϩ signals into the mitochondrial matrix, which, depending on the exact conditions, can lead to enhanced ATP synthesis or the initiation of apoptotic signaling (7). IP 3 R channel activity is primarily regulated by IP 3 and Ca 2ϩ concentrations, although the channel is also modulated by phosphorylation (8), ATP (9), and interaction with a large number of proteins (10).…”

Functional Inositol 1,4,5-Trisphosphate Receptors Assembled from Concatenated Homo- and Heteromeric Subunits

“…Early reports have suggested that their sensitivity to Ca 2ϩ is greater for IP 3 R3 than IP 3 R1; however, all three subtypes show a bell-shaped Ca 2ϩ dependence with the optimum cytosolic [Ca 2ϩ ] around 200 nM (26,29,30). In addition, IP 3 R subtypes are modulated differentially by kinases, phosphatases, proteolysis, transcriptional, post-transcriptional, and post-translational modifications (31)(32)(33)(34)(35)(36)(37)(38)(39). Consequently, it is widely held that these differences may underlie subtype-specific Ca 2ϩ patterns, and it follows that the particular cellular complement of IP 3 Rs may therefore dictate the spatio-temporal patterns of Ca 2ϩ signals evoked in response to IP 3 formation in an individual cell (13, 35, 40 -42).…”

“…The activity of individual homotetramers has been interrogated using single channel electrophysiology or fluorescence-based experiments providing fundamental information regarding the binding of IP 3 , together with the gating and regulation of the activity of individual IP 3 R subtypes (19,25,35,45). However, because virtually all cells express a complement of at least two IP 3 R subtypes, it is predicted that most cells express a combination of homo-and heterotetrameric channels (13,14,18).…”

Inositol 1,4,5-trisphosphate receptors in the endoplasmic reticulum: A single-channel point of view

“…It is therefore not surprising that it has been the subject of intense study ever since its identification [3]. Many aspects of the InsP 3 R channel have been extensively reviewed recently, including its molecular structure [4–7] and its regulation by phosphorylation [8], redox reagents [9, 10] and ATP [8]. Thus, this short review will focus on the more fundamental properties of the single InsP 3 R channel: its ion conductance properties and its regulation by its physiological ligands—InsP 3 and Ca 2+ , especially those reported since our previous reviews of single InsP 3 R channel properties [11, 12].…”