Thomas Braulke and Stephan Storch; University Medical Center Hamburg-Eppendorf, Dept. Biochemistry, Children's Hospital

Intracellular transport, retention and degradation of GlcNac-1-phosphotransferase in the Golgi apparatus

Mucolipidoses II and II are autosomally recessive inherited lysosomal storage disorders which are caused by deficiency of the Golgi-localized, hexameric GlcNac-1-phosphotransferase complex. GlcNac-1-phosphotransferase is the key enzyme catalyzing the formation of the mannose 6-phosphate recognition marker on newly synthesized soluble lysosomal hydrolases required for their efficient transport to lysosmes. The aim of this project is the identification of sorting signals in the cytoplasmic domains of the α and β-subunits of GlcNac-1-phosphotransferase, cytosolic interaction partners and their significance for vesicular sorting between the endoplasmic reticulum and the Golgi complex. Furthermore, proteins required for retrograde transport and retention of GlcNac-1-phosphotransferase in Golgi subcompartments will be analysed as well as the role of GlcNac-1-phosphotransferase domains for assembly of the complex.


Paul Saftig and Michael Schwake, Institute of Biochemistry, University of Kiel

Lysosomal membrane proteins and mannose-6-phosphate receptor independent transport to the lysosome

We could recently identify a new pathway for protein sorting to the lysosome (Cell, 131,770-783,2007). The lysosomal enzyme β-glucocerebrosidase - the enzyme defective in patients with the most common lysosomal storage disease (Gaucher Disease)- is delivered to the lysosome through its interaction with the transmembrane protein LIMP-2. We plan to understand this pathway, the new receptor-ligand interaction but also potential novel interacting proteins in more detail. In addition the role of other lysosomal membrane proteins in lysosomal biogenesis will be in the focus of our interest.


Tim-Wolf Gilberger, Bernhard-Nocht-Institute

Golgi organisation and trans-Golgi sorting in the malaria parasite

The invasion, transformation and destruction of erythrocytes are responsible for the pathobiology of a malaria infection. P. falciparum, the causative agent, relies on a sophisticated protein secretion system that enables the parasite to traffic proteins to numerous compartments within the cell and further into the host cell cytoplasm and surface. The aim of this project is to elucidate the Golgi architecture and the mechanism of protein trafficking within the trans-Golgi network of the pathogen using genetically modified parasites and live microscopy.


Martin Aepfelbacher, University Medical Center Hamburg-Eppendorf, Institite of Microbiology and Virology

Intracellular complexes and transport during bacterial infection

Unique intracellular signal complexes are assembled at the contact site of pathogenic bacteria with host cells during bacterial invasion or phagocytosis. We study the transport of regulators of the Rho GTPase family (i.e. CDC42GAP) to the bacteria loaded phagosome and its function in immune cells. Some bacterial pathogens block immune reactions by interfering with intracellular transport events. We are interested in the intracellular transport of a Yersinia virulence factor (YopM) to the nucleus and its consequence for the infection process. A combination of microbiological, immunological and cell biological techniques is applied to study these events.


Markus Glatzel, University Medical Center Hamburg-Eppendorf, Institute of Neuropathology

Exosomal transport of prions

Prion diseases are fatal neurodegenerative disorders which are transmissible. An essential part of the infectious agent, termed the prion, is composed of an abnormal isoform of the host-encoded cellular prion-protein termed PrPSc. The molecular details underlying PrPSc formation and the mechanisms involved in the spread of infectious prions within affected hosts and from donor to host are poorly understood. Recently, exosomes have been shown to mobilize PrPSc as well as prion infectivity. Moreover retroviral infection increases exosome formation and virions have been shown to contain PrPSc. The project focus on the investigation of the role of exosomes in secretion of cellular- and disease-associated forms of the prion protein.


Kerstin Kutsche, University Medical Center Hamburg-Eppendorf, Institute of Human Genetics

OCRL-mediated vesicular transport

Mutations of OCRL cause the oculo-cerebro-renal syndrome of Lowe (LS), an X-linked disorder characterized by congenital cataracts, renal Fanconi syndrome, and mental retardation. OCRL is a catalytically active phosphoinositide 5-phosphatase with phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] as the preferred substrate. Recently, OCRL has been implicated in membrane trafficking from endosomes to the Golgi apparatus as well as in early steps of the endocytic pathway. We use primary fibroblast cells of patients with LS that are deficient of OCRL to study (1) subcellular distribution of PtdIns(4,5)P2 and (2) possible defects in endocytosis and recycling of various cell-surface receptors.


Hans-Jürgen Kreienkamp, University Medical Center Hamburg-Eppendorf, Institute of Human Genetics

Regulated sorting of plasma membrane receptors through the Golgi-associated protein PIST

The Golgi-associated protein PIST/GOPC is involved in the sorting and intracellular transport of various receptor proteins. The activity of PIST is controlled by the small GTPase Tc10. We will elucidate how the subcellular distribution of PIST-associated membrane proteins is affected by the activity of Tc10. We are interested to identify signalling pathways which - via Tc10/PIST - control the availibility of cell surface receptors at the plasma membrane. In addition, we will investigate the function of PIST in neurons, in particular with respect to the targeting of receptors to postsynaptic sites. These projects will involve modern microscopic methods and live cell imaging.


Jõrg Heeren, University Medical Center Hamburg-Eppendorf, Institute of Biochemistry; Molecular Cell Biology, University Medical Center Hamburg-Eppendorf

Regulation of endosomal LRP1 transport

Abnormalities in lipoprotein metabolism are associated with the development of atherosclerosis and the metabolic syndrome. The uptake and intracellular processing of lipoproteins directly influence the plasma lipoprotein levels and both processes are mediated by hepatic lipoprotein receptors such as the LDL receptor and the LDL receptor-related protein 1 (LRP1). Next to triglyceride-rich lipoproteins, LRP1 can also bind to various other ligands indicating that different effects are mediated by specific LRP1 adaptor proteins. In this project we want to investigate how LRP1-specific adaptor proteins modulate LRP1 function with the focus on internalisation and endosomal trafficking.