The continuing disappearance of pure Ca2+ buffers

Advances in the understanding of a class of Ca2+-binding proteins usually referred to as Ca2+ buffers are reported. Proteins historically embraced within this group include parvalbumins (alpha and beta), calbindin-D9k, calbindin-D28k and calretinin. Within the last few years a wealth of data has accumulated that allow a better understanding of the functions of particular family members of the > 240 identified EF-hand Ca2+-binding proteins encoded by the human genome. Studies often involving transgenic animal models have revealed that they exert their specific functions within an intricate network consisting of many proteins and cellular mechanisms involved in Ca2+ signaling and Ca2+ homeostasis, and are thus an essential part of the Ca2+ homeostasome. Recent results indicate that calbindin-D28k, possibly also calretinin and oncomodulin, the mammalian beta parvalbumin, might have additional Ca2+ sensor functions, leaving parvalbumin and calbindin-D9k as the only pure Ca2+ buffers.