Organellar Calcium Buffers

Ca 2þ is an important intracellular messenger affecting many diverse processes.In eukaryotic cells, Ca 2þ storage is achieved within specific intracellular organelles, especially the endoplasmic/sarcoplasmic reticulum, in which Ca 2þ is buffered by specific proteins known as Ca 2þ buffers.Ca 2þ buffers are a diverse group of proteins, varying in their affinities and capacities for Ca 2þ , but they typically also carry out other functions within the cell.The wide range of organelles containing Ca 2þ and the evidence supporting cross-talk between these organelles suggest the existence of a dynamic network of organellar Ca 2þ signaling, mediated by a variety of organellar Ca 2þ buffers. INTRACELLULAR Ca 2þ DYNAMICSC a 2þ serves as an intracellular messenger in various cellular processes, including muscle contraction, gene expression, and fertilization (Berridge et al. 2003).To use Ca 2þ , the cell requires a readily mobilizable source of Ca 2þ , the majority of which is found within the lumen of the endoplasmic reticulum (ER) and/or sarcoplasmic reticulum (SR), but is also located in the Golgi apparatus, peroxisomes, mitochondria, and endolysosomal compartments.It is not surprising that Ca 2þ levels are of central importance in dictating the function of proteins that reside in intracellular organelles.Although some Ca 2þ exists as free ions within these compartments, much of it is buffered by specific proteins, simply known as Ca 2þ buffers.However, these proteins are diverse in terms of structure, oligomerization, affinity and capacity for Ca 2þ , and physical basis for binding Ca 2þ ions, one commonality across Ca 2þ buffers is that they also serve other roles within the cell.These roles include catalyzing the correct folding of other cellular proteins, regulating Ca 2þ release and retention, and communicating information about Ca 2þ levels within organelles to other proteins. ENDOPLASMIC RETICULUMThe ER is a multifunctional organelle within the eukaryotic cell that serves as the single largest Ca 2þ store inside nonstriated muscle cells.The ER is also responsible for functions as diverse as protein synthesis and posttranslational modification, lipid and steroid metabolism, and drug detoxification (Michalak and Opas 2009).Within the ER lumen, the total concentration of Ca 2þ is approximately 1 mM, with free Ca 2þ in the range of approximately 200 mM and the remainder buffered via ER resident proteins (Michalak and Opas 2009).Most ER Ca 2þ