A5021030878- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Calcium signaling and nucleotide metabolism
- Lipid Membrane Structure and Behavior
- Autophagy in Disease and Therapy
- Lysosomal Storage Disorders Research
- Fungal and yeast genetics research
- Retinal Development and Disorders
- Erythrocyte Function and Pathophysiology
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Pancreatic function and diabetes
- Microtubule and mitosis dynamics
- Photosynthetic Processes and Mechanisms
- Biotin and Related Studies
- ATP Synthase and ATPases Research
- RNA Interference and Gene Delivery
- Genetic Neurodegenerative Diseases
- Plant Reproductive Biology
- Trypanosoma species research and implications
- Mosquito-borne diseases and control
- DNA Repair Mechanisms
- Protein Structure and Dynamics
- Heat shock proteins research
- PI3K/AKT/mTOR signaling in cancer
Osnabrück University
2016-2025
Heidelberg University
2001-2006
Technical University of Munich
2006
Dartmouth College
1997-2005
Columbia University
2005
California Institute of Technology
2005
University of Geneva
2005
Nierenzentrum Heidelberg
2004
Johns Hopkins University
2001
University of Oregon
1999
Membrane fusion within the eukaryotic endomembrane system depends on initial recognition of Rab GTPase transport vesicles by multisubunit tethering complexes and subsequent coupling to SNARE-mediated fusion. The conserved vacuolar/lysosomal homotypic vacuole protein sorting (HOPS) complex combines both activities. Here we present overall structure fusion-active HOPS complex. Our data reveal a flexible ≈30-nm elongated seahorse-like structure, which can adopt contracted shapes. Surprisingly,...
The autophagy-related (Atg) proteins play a key role in the formation of autophagosomes, hallmark autophagy. function cluster composed by Atg2, Atg18, and transmembrane Atg9 is completely unknown despite their importance In this study, we provide insights into molecular these identifying characterizing Atg2 point mutants impaired binding. We show that associates to autophagosomal membranes through lipid binding independently from Atg9. Its interaction with Atg9, however, for confinement...
The entry of segments preproteins defined lengths into the matrix space mitochondria was studied. mitochondrial chaperone Hsp70 (mtHsp70) interacted with proteins emerging from protein import channel and stabilized translocation intermediates across membranes in an adenosine triphosphate-dependent fashion. bound to presequence mature parts preproteins. In absence mtHsp70 binding, less than 30 40 residues diffused out mitochondria. Thus, reversible up a late stage. channels both constitute...
Homotypic vacuole fusion in yeast requires Sec18p (N-ethylmaleimide–sensitive protein [NSF]), Sec17p (soluble NSF attachment [α-SNAP]), and typical vesicle (v) target membrane (t) SNAP receptors (SNAREs). We now report that vacuolar v- t-SNAREs are mainly found with as v–t-SNARE complexes vivo on purified vacuoles rather than only transiently forming such during docking, disrupting them upon fusion. In the priming reaction, ATP dissociate this complex, accompanied by release of Sec17p. SNARE...
The homotypic fusion of yeast vacuoles requires Sec18p (NSF)-driven priming to allow vacuole docking, but the mechanism that links and docking is unknown. We find a large multisubunit protein called Vam2/6p complex bound cis-paired SNAP receptors (SNAREs) on isolated vacuoles. This association with cis-SNARE disrupted during priming. then binds Ypt7p, guanosine triphosphate binding Rab family, initiate productive contact between Thus, complexes can contain Rab/Ypt effectors, these effectors...
Within the endomembrane system of eukaryotic cells, multisubunit tethering complexes together with their corresponding Rab-GTPases coordinate vesicle and fusion. Here, we present evidence that two homologous hexameric complexes, endosomal CORVET (Class C core vacuole/endosome transport) vacuolar HOPS (homotypic vacuole fusion protein sorting) complex, have similar subunit topologies. Both contain Rab-binding proteins at one end, Sec1/Munc18-like Vps33 opposite side, suggesting a model on...
Membrane fusion along the endocytic pathway occurs in a sequence of tethering, docking, and fusion. At endosomes vacuoles, CORVET (class C core vacuole/endosome tethering) HOPS (homotypic vacuole protein sorting) tethering complexes require their organelle-specific Rabs for localization function. Until now, despite absence experimental evidence, it has been assumed that is membrane-tethering factor. To test this theory understand mechanistic analogies with complex, we set up an vitro system,...
For their function in fusion and signaling, Rab GTPases need to be converted into active GTP form. We previously identified the conserved Mon1-Ccz1 complex as guanine nucleotide exchange factor (GEF) of yeast Rab7 GTPase Ypt7. To address possible GEF mechanism, we generated a homology model predicted longin domains Mon1 Ccz1 using template Rab-binding surface TRAPP complex. Based on this, mutations both that block Ypt7 activation, without affecting heterodimer formation intracellular...
During autophagy, a newly formed double membrane surrounds its cargo to generate the so-called autophagosome, which then fuses with lysosome after closure. Previous work implicated that endosomal Rab7/Ypt7 associates autophagosomes prior their fusion lysosomes. Here, we unravel how Mon1-Ccz1 guanosine exchange factor (GEF) acting upstream of Ypt7 is specifically recruited pre-autophagosomal structure under starvation conditions. We find directly binds Atg8, yeast homolog members mammalian...