The Making and Breaking of Inositol 1,4,5-Trisphosphate Receptor Tetramers.

Mammalian cells express three highly conserved inositol 1,4,5-trisphosphate (IP3) receptor types (IP3R1, IP3R2 and IP3R3), which have broadly similar characteristics, but markedly different distributions, and form homo- or heterotetrameric Ca2+ channels in endoplasmic reticulum (ER) membranes. A vast array of published work details how mature, ER membrane-located IP3 receptor tetramers are regulated, but much less attention has been paid to the intriguing questions of how the tetramers are assembled and destroyed as part of their natural life cycle. Are they assembled at the ER membrane from nascent, or completely translated polypeptides? How are they disassembled and degraded? These questions and other recently defined modes of IP3 receptor processing will be briefly reviewed.