Calmodulin as a protein linker and a regulator of adaptor/scaffold proteins

Calmodulin (CaM) is a universal regulator for a huge number of proteins in all eukaryotic cells. Best known is its function as a calcium-dependent modulator of the activity of enzymes, such as protein kinases and phosphatases, as well as other signaling proteins including membrane receptors, channels and structural proteins. However, less well known is the fact that CaM can also function as a Ca2+-dependent adaptor protein, either by bridging between different domains of the same protein or by linking two identical or different target proteins together. These activities are possible due to the fact that CaM contains two independently-folded Ca2+ binding lobes that are able to interact differentially and to some degree separately with targets proteins. In addition, CaM can interact with and regulates several proteins that function exclusively as adaptors. This review provides an overview over our present knowledge concerning the structural and functional aspects of the role of CaM as an adaptor protein and as a regulator of known adaptor/scaffold proteins.The work in the authors laboratories were funded by grant SAF2014-52048-R from the Secretaría de Estado de Investigación, Desarrollo e Innovación (to AV); the Danish Research Council DFF- 4004-00560, the AP Møller Foundation, Dagmar Marshalls Foundation, Einar Willumsen Foundation, Aase and Ejnar Danielsen Foundation, Wedell Wedellsborg Foundation, Frænkels Foundation and Danish Heart Foundation 13-04-R94-A4547-2280 (to MWB); and the National Sciences and Engineering Research Council of Canada RGPIN/05977-2015 (to HJV).Peer reviewe