The divalent cation, Ca++, is one of the most versatile essential substances for living organisms - on the one hand forming rigid extracellular matrices such as bone while on the other acting as one of the major intra- and extra-cellular regulatory signals for numerous bilogical processes. It is now clear that families of proteins have evolved with specialized structures which dictate their calcium binding properties and functions. This proposal requests partial support for the fourth in a series of international symposia on "Calcium Binding Proteins in Health and Diseases" which, since their inception in 1974, have provided the major forum for considering the diverse aspects of calcium function. The proposed program includes a mixture of formal presentations, round table discussions, and poster presentations devoted to considering the structure, function, genetic organization and expression of both extracellular (low affinity) and intracellular (high affinity) Ca++ binding proteins. Considerations of low affinity Ca++ interactions will include discussion of: 1) Ca++ proteolipid interaction; 2) Ca++ deposition; 3) Vitamin K-dependent formation of Gamma-carboxyglutamic acid residues in proteins; 4) Gla-containing clotting factors; and, 5) Other Ca++ dependent proteases. A number of sessions will be devoted to discussing current studies of high affinity "hand" containing calcium binding proteins which act as intracellular regulators, particularly calmodulin and troponin C. Substantial consideration also will be given to the regulation of Ca++ homeostasis with sessions devoted to: 1) Vitamin D-dependent Ca++ uptake systems; 2) Ca++ influx-release mechanisms; and, 3) Ca++ sequestration systems including membrane Ca++ ATPases. As a conclusion to this symposium, the integration of Ca++ dependent regulation and other cellular signalling systems, such as the cyclic nucleotides, will be considered in a session devoted to the regulation of complex metabolic processes. Clearly, the content of this symposium will have relevance to a variety of disease processes such as neoplasia, hemophilia and related circulatory disorders, muscle and neurological disorders, metabolic dysfunctions, and diseases induced by dietary deficiencies.