Calnuc, a Golgi Ca²⁺-binding Protein that Binds Gα Subunits

Calnuc is a protein that has regions of high homology to calreticulin. Calnuc is unusual in that it is the only protein identified so far that can bind both Ca²⁺ and heterotrimeric G protein alpha subunits. We have previously shown that, like calreticulin, calnuc is present both in the cytoplasm and in the Golgi lumen of all cell types. We have also demonstrated that the cytoplasmic pool of calnuc binds to Gαi3 on the cytoplasmic surface of the Golgi, and the Golgi pool is localized in the cis Golgi cisternae where it constitutes the major Ca²⁺ binding protein in the Golgi and represents a major Ca²⁺ storage pool. It is the most abundant Golgi protein based on proteomic analyses of in rat liver Golgi fractions. Calnuc is a resident Golgi protein with a half-life in the Golgi of 8-24 hr, but it can also be released from the cell as it has been found in the sera of mice prone to the autoimmune disorder systemic lupus erythematosis and is released into the medium of cultured cells where it may influence cell behavior.

Thus calnuc is an unusual protein with three different fates. Our current projects focus on trying to unravel the mysteries of calnuc’s role and binding partners in the Golgi as well as to understand its extracellular functions and its role in in regulation of Gαi3.