CHARITÉ BERLIN INVESTIGACIÓN GENÉTICA – PROYECTO DANZA
INSTITUTO DE MEDICINA Y GENÉTICA HUMANA

PROYECTO DE INVESTIGACIÓN MÉDICA Y DANZA

DR. PETER KRAWITZ - Universidad de Medicina Charité en Berlín

Ispasión Productions colaboró con Herr Dr. Peter Krawitz del Instituto Médico de Genética Humana en Charité, Berlín, en su nuevo estudio médico de una enfermedad rara en la genética humana (deficiencias de anclaje GPI).

En este proyecto artístico de danza médica, los bailarines representaron a través de rutinas de danza contemporánea, en 3 actos de vídeo de danza, tres de los diferentes estados de la genética humana.

El primer acto muestra un comportamiento normal y saludable de la genética humana, mientras que el segundo acto muestra un comportamiento defectuoso de la genética humana que conduce al cuerpo a esta rara enfermedad.

VIDEOS


1- GPI: ANCHOR SYNTHESIS

(Synthesis of GPI-anchor)

(explicación original en ingles)

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.

2- ANCHOR DEFICIENCY

(Deficiency of anchor syntesis)

(explicación original en ingles)

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.

3- ATTACK OF THE SECRETASE

(Attack of the Phospholipase)

(explicación original en ingles)

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.

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