Charakterisierung extrazellulärer, Calcium-bindender Proteine, Molekulare Neurobiologie

Interactions between cells and their environment play crucial roles both during development and also for the maintainance of functional structures in the adult organism. On the molecular level these interactions are mediated by cellular receptors and molecules of the extracellular matrix. We are interested in a certain family of matrix proteins, the so called EC domain proteins. The members of these family are multidomain proteins characterised by a domain which contains two calcium-binding EF-hand motifs and was therefore termed extracellular calcium-binding (EC) domain. The prototype of these family is BM-40 (also called osteonectin or SPARC), a glycoprotein that has been implicated in cell growth and tissue remodeling. It consists of three domains, a N-terminal acidic one followed by a domain homologous to follistatin (FS domain) and a C-terminal EC domain. BM-40 was the first extracellular protein that was shown to contain EF-hand motifs, demonstrating that this motif is not confined to intracellular proteins. EC domains are also found in the proteins SC1/hevin, tsc36 and testican/Spock where they are always preceded by a FS domain. During the last years we could identify four novel members of the EC domain family. Two share the domain organisation of testican/Spock and hence were termed testican-2 and testican-3. The two other proteins show a unique domain organisation and were termed SMOC-1 and SMOC-2, where SMOC stands for Secreted Modular Calcium-binding protein.

FS represents the follistatin-like domain, TY the thyroglobulin-like domain and EC the extracellular calcium-binding domain. Black bars within the EC domain refers to the EF-hand motifs. A domain with partial similarity to von Willebrand factor type C domains is indicated by vWC. TCAN and SMOC denote the domains only found in testicans and SMOC-1 and -2, respectively. Triangles indicate putative glycosaminoglycan attachment sites in testicans. Domains with no homology to other proteins are shown as open boxes. Signal peptides are not shown.