Research topic: Lysosomal sorting
Main topics are:
1. Analysis of GGA structure (ubiquitin binding domain) and function for the lysosomal enzyme sorting and autophagy in neurons
2. Analysis of the cargo recognition motifs in LERP
The classical item for lysosomes reduced them to ”degradative and waste recycling organelles”, characterised by the rare specific lysosomal storage diseases. In recent years, however, lysosomes have been recognized as active participants in cellular metabolic processes, in signalling nutrition status and growth and in apoptosis of cells. Their dysfunction has been detected in many neurological diseases causing disturbed autophagy. The resulting aggregates are blocking the metabolism and the providing of monomers for reuse.
In mammalian cells two mannose-6-phosphate-receptors (MPR) are sorting the lysosomal acid hydrolases to lysosomes by interaction with specific sorting adaptors. These include three different Golgi-adaptor proteins (GGAs). The recognition motifs for interaction have been established, however, the specific meaning of the three single GGAs for sorting requires further analyses. We found that in Drosophila a similar system with only one lysosomal enzyme receptor protein (LERP) and only one GGA exists with high GGA levels in pigment cells of the retina and the mushroom bodies which are involved in the chemosensory memory and learning in insects. Ubiquitious and eye-specific GGA-knockdown by RNAi in fly as well as modulation of the expression levels resulted in impaired lysosomal sorting and disturbed LERP trafficking. To establish these findings a knockout is done using the CRISPR/CAS system in fly for GGA and LERP.
1. Analysis of GGA structure (ubiquitin binding domain) and function for the lysosomal enzyme sorting and autophagy in neurons
2. Analysis of the cargo recognition motifs in LERP
The classical item for lysosomes reduced them to ”degradative and waste recycling organelles”, characterised by the rare specific lysosomal storage diseases. In recent years, however, lysosomes have been recognized as active participants in cellular metabolic processes, in signalling nutrition status and growth and in apoptosis of cells. Their dysfunction has been detected in many neurological diseases causing disturbed autophagy. The resulting aggregates are blocking the metabolism and the providing of monomers for reuse.
In mammalian cells two mannose-6-phosphate-receptors (MPR) are sorting the lysosomal acid hydrolases to lysosomes by interaction with specific sorting adaptors. These include three different Golgi-adaptor proteins (GGAs). The recognition motifs for interaction have been established, however, the specific meaning of the three single GGAs for sorting requires further analyses. We found that in Drosophila a similar system with only one lysosomal enzyme receptor protein (LERP) and only one GGA exists with high GGA levels in pigment cells of the retina and the mushroom bodies which are involved in the chemosensory memory and learning in insects. Ubiquitious and eye-specific GGA-knockdown by RNAi in fly as well as modulation of the expression levels resulted in impaired lysosomal sorting and disturbed LERP trafficking. To establish these findings a knockout is done using the CRISPR/CAS system in fly for GGA and LERP.