Apocalmodulin

Intracellular Ca2+ is normally maintained at submicromolar levels but incre ases during many forms of cellular stimulation. This increased Ca2+ binds t o receptor proteins such as calmodulin (CaM) and alters the cell's metaboli sm and physiology. Calcium-CaM binds to target proteins and alters their fu nction in such a way as to transduce the Ca2+ signal. Calcium-free or apoca lmodulin (ApoCaM) binds to other proteins and has other specific effects, A pocalmodulin has roles in the cell that apparently do not require the abili ty to bind Ca2+ at all, and these roles appear to be essential for life. Ap ocalmodulin differs from Ca2+-CAM in its tertiary structure. It binds targe t proteins differently, utilizing different binding motifs such as the IQ m otif and noncontiguous binding sites. Other kinds of binding potentially aw ait discovery. The ApoCaM-binding proteins are a diverse group of at least 15 proteins including enzymes, actin-binding proteins, as well as cytoskele tal and other membrane proteins, including receptors and ion channels. Much of the cellular CaM is bound in a Ca2+-independent manner to membrane stru ctures within the cell, and the proportion bound changes with cell growth a nd density, suggesting it may be a storage form. Apocalmodulin remains tigh tly bound to other proteins as subunits and probably hastens the response o f these proteins to Ca2+. The overall picture that emerges is that CaM cycl es between its Ca2+-bound and Ca2+-free states and in each state binds to d ifferent proteins and performs essential functions. Although much of the re search focus has been on the roles of Ca2+-CaM, the roles of ApoCaM are equ ally vital but less well understood.