IP3R1IP3R3

IP3R1IP3R3 refers to heteromeric assemblies of inositol 1,4,5-trisphosphate receptors that contain both IP3 receptor type 1 (IP3R1) and type 3 (IP3R3) subunits. In mammalian cells, IP3 receptors form tetrameric Ca2+ release channels on the endoplasmic reticulum. Subunits of the IP3R family can assemble as homo- or heterotetramers, and the inclusion of IP3R1 with IP3R3 endows channels with distinct regulatory properties compared with homomeric receptors.

Activation requires binding of IP3 to the IP3-binding domains, opening the channel and releasing Ca2+ from the ER. Channel activity is modulated by cytosolic Ca2+ in a biphasic manner, with IP3R heterotetramers often showing intermediate sensitivities to IP3 and Ca2+ and different responses to ATP and accessory proteins relative to IP3R1 or IP3R3 homotetramers.

IP3R1 is highly expressed in brain; IP3R3 is more broadly expressed; co-expression and heteromerization occur in several tissues, including neurons, where IP3R1/IP3R3 channels shape spatiotemporal Ca2+ signals that control secretion, neuronal excitability, and gene expression. Distinct Ca2+ signal patterns arise from heterotetramers, influencing CICR dynamics and downstream processes.

Interactions with regulatory proteins such as Bcl-2 family proteins and IRBIT modulate IP3R gating and sensitivity. Alterations in IP3R1/IP3R3 function have been implicated in neurological disorders and in dysregulated Ca2+ signaling, though the specific contribution of IP3R1IP3R3 heteromers remains an active area of research.