Institut für Medizinische Genetik und Humangenetik
Orellana & Fernández collaborated with Herr Dr. Peter Krawitz from the Medical Institute for Human Genetic in Charité, Berlin, in his new medical study of a rare disease in the human genetic ( GPI-anchor deficiencies ).
In these artistic medical-dance project, Orellana & Fernández represented through contemporary dance routines in 3 dance video acts, three of the different states of the human genetics. The first act shows a normal and healthy behaviour of the human genetics, while the second act shows a defective behaviour of the human genetics that leads the body to this rare disease.
In total there are three mannose residues and three ethanolamins that have to be attached to the phosphoinositol in the membrane to form the GPI-anchor. The enzymes that are involved this synthesis are encoded by the «PIG» genes. The mannose residues for example are added by PIGM, PIGV, and PIGB. When the GPI-anchor is complete, it is linked to a substrate. The covalent bond is formed between an ethanolamin and the C-terminus of a protein. The transamidase is the enzyme that catalyzes this reaction. By this means a protein can be attached to the cell surface.
About 30 genes are involved in the synthesis of the GPI-anchor and pathogenic mutations have been identified in several of them. Mutations in PIGV for instance impair the attachment of the second mannose residue, whereas mutations in PIGO inhibit the transfer of an ethanolamine. Whenever a defect in such genes hinders the complete synthesis of the GPI-anchor, a protein is not properly linked to the cell surface and is lost into the lumen. The enzyme alkaline phosphatase for example is such a GPI-linked substrate. In Mabry syndrome, which is also caused by mutations in PIGV and PIGO, the enzyme is secreted. This results in hyperphosphatasia, which is a pathognomonic finding in this disorder.
As soon as the GPI-anchored proteins reach the cell surface, they group together in lipid rafts.Their close proximity is enabled by modifications to the fatty acids that are catalyzed by «post GPI attachment proteins» or short PGAP1-3. Mutations in these genes may disturb this organization and the distances between GPI-anchored substrates increases. This makes the link between anchor and substrate more prone to cleavage by a secretase, such as the phospholipase D. The consequences are similar to defects in the late anchor synthesis. A higher proportion of substrate is lost to the serum.