A5002815807- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Lipid Membrane Structure and Behavior
- Calcium signaling and nucleotide metabolism
- Cellular Mechanics and Interactions
- Lysosomal Storage Disorders Research
- Ubiquitin and proteasome pathways
- Erythrocyte Function and Pathophysiology
- Protein Kinase Regulation and GTPase Signaling
- Fungal and yeast genetics research
- RNA Research and Splicing
- Advanced Proteomics Techniques and Applications
- Retinal Development and Disorders
- Amino Acid Enzymes and Metabolism
- Microtubule and mitosis dynamics
- Pancreatic function and diabetes
- Metabolism and Genetic Disorders
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
- Enzyme Structure and Function
- Cancer, Hypoxia, and Metabolism
- Neurobiology and Insect Physiology Research
- Biomedical Research and Pathophysiology
- Photosynthetic Processes and Mechanisms
Innsbruck Medical University
2015-2025
Universität Innsbruck
2015-2025
Institute of Cell Biology
2024
Cornell University
2007-2023
Austrian Drug Screening Institute (Austria)
2015-2017
Vienna Biocenter
2014
Co-operative College
2014
Max Planck Unit for Structural Molecular Biology
2004
Research Institute of Molecular Pathology
2001-2002
University of Graz
2002
The extracellular signal-regulated kinase (ERK) cascade regulates proliferation, differentiation, and survival in multicellular organisms. Scaffold proteins regulate intracellular signaling by providing critical spatial temporal specificity. scaffold protein MEK1 (mitogen-activated ERK 1) partner (MP1) is localized to late endosomes the adaptor p14. Using conditional gene disruption of p14 mice, we now demonstrate that p14–MP1-MEK1 complex endosomal traffic cellular proliferation. This...
We have identified a novel, highly conserved protein of 14 kD copurifying with late endosomes/lysosomes on density gradients. The protein, now termed p14, is peripherally associated the cytoplasmic face in variety different cell types. In two-hybrid screen p14 as bait, we mitogen-activated kinase (MAPK) scaffolding MAPK/extracellular signal–regulated (ERK) (MEK) partner 1 (MP1) an interacting protein. confirmed specificity this interaction vitro by glutathione S-transferase pull-down assays...
Five endosomal sorting complexes required for transport (ESCRTs) mediate the degradation of ubiquitinated membrane proteins via multivesicular bodies (MVBs) in lysosomes. ESCRT-0, -I, and –II interact with cargo on endosomes. ESCRT-II also initiates assembly a ringlike ESCRT-III filament consisting Vps20, Snf7, Vps24, Vps2. The AAA–adenosine triphosphatase Vps4 disassembles recycles complex, thereby terminating ESCRT pathway. A mechanistic role intraluminal vesicle (ILV) formation has been...
The ESCRT machinery mediates reverse membrane scission. By quantitative fluorescence lattice light-sheet microscopy, we have shown that ESCRT-III subunits polymerize rapidly on yeast endosomes, together with the recruitment of at least two Vps4 hexamers. During their 3-45 s lifetimes, assemblies accumulated 75-200 Snf7 and 15-50 Vps24 molecules. Productive budding events required additional Membrane was associated continuous, stochastic exchange components, rather than steady growth fixed...
The degradation and recycling of cellular components is essential for cell growth survival. Here we show how selective non-selective lysosomal protein pathways cooperate to ensure survival upon nutrient limitation. A quantitative analysis starvation-induced proteome remodeling in yeast reveals comprehensive changes already the first three hours. In this period, many different integral plasma membrane proteins undergo endocytosis vacuoles via multivesicular body (MVB) pathway. Their becomes...
Cell migration is mediated by the dynamic remodeling of focal adhesions (FAs). Recently, an important role endosomal signaling in regulation cell was recognized. Here, we show essential function for late endosomes carrying p14-MP1 (LAMTOR2/3) complex FA dynamics. p14-MP1-positive move to periphery along microtubules (MTs) a kinesin1- and Arl8b-dependent manner. There they specifically target FAs regulate turnover, which required migration. Using genetically modified fibroblasts from...
Cellular homeostasis requires the ubiquitin-dependent degradation of membrane proteins. This was assumed to be mediated exclusively either by endoplasmic reticulum-associated (ERAD) or endosomal sorting complexes required for transport (ESCRT)-dependent lysosomal degradation. We identified in Saccharomyces cerevisiae an additional pathway that selectively extracts proteins at Golgi and endosomes cytosolic proteasomes. One endogenous substrate this endosome Golgi-associated (EGAD) is...
Eukaryotic genomes are organized within the nucleus through interactions with inner nuclear membrane (INM) proteins. How chromatin tethering to INM is controlled in interphase and how this process contributes subsequent mitotic envelope (NE) remodeling remains unclear. We have probed these fundamental questions using fission yeast Schizosaccharomyces japonicus, which breaks reforms NE during mitosis. show that attachments between heterochromatin transmembrane Lem2-Nur1 complex at remodeled...
Phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P(2)] regulates several vacuolar functions, including acidification, morphology, and membrane traffic. The lipid kinase Fab1 converts phosphatidylinositol-3-phosphate [PtdIns(3)P] to PtdIns(3,5)P(2). PtdIns(3,5)P(2) levels are controlled by the adaptor-like protein Vac14 Fig4 PtdIns(3,5)P(2)-specific 5-phosphatase. Interestingly, serve a dual function: they both implicated in synthesis turnover of an unknown mechanism. We now show that Fab1,...
Mitogen-activated protein kinase (MAPK) signaling is regulated by assembling distinct scaffold complexes at the plasma membrane and on endosomes. Thus, spatial resolution might be critical to determine specificity. Therefore, we investigated whether epidermal growth factor receptor (EGFR) traffic through endosomal system provides information for MAPK signaling. To mislocalize late endosomes cell periphery used dynein subunit p50 dynamitin. The peripheral translocation of resulted in a...
The unconventional secretory pathway exports proteins that bypass the endoplasmic reticulum. In Saccharomyces cerevisiae, conditions trigger Acb1 secretion via this generate a Grh1 containing compartment composed of vesicles and tubules surrounded by cup-shaped membrane collectively called CUPS. Here we report quantitative assay for reveals requirements ESCRT-I, -II, -III but, surprisingly, without involvement Vps4 AAA-ATPase. major ESCRT-III subunit Snf7 localizes transiently to CUPS was...
Cellular adaptation in response to nutrient limitation requires the induction of autophagy and lysosome biogenesis for efficient recycling macromolecules. Here, we discovered that starvation TORC1 inactivation not only lead up-regulation vacuole proteins involved but also result down-regulation many membrane supply amino acids as part a remodeling process. Down-regulation is initiated by ubiquitination, which accomplished coordination multiple E3 ubiquitin ligases, including Rsp5, Dsc...
Signaling pathways in eukaryotic cells are often controlled by the formation of specific signaling complexes, which coordinated scaffold and adaptor proteins. Elucidating their molecular architecture is essential to understand spatial temporal regulation cellular signaling. p14 MP1 form a tight ( K d = 12.8 nM) endosomal adaptor/scaffold complex, regulates mitogen-activated protein kinase (MAPK) Here, we present 1.9-Å crystal structure biologically functional p14/MP1 complex. The overall...
In this work, we evaluate the incorporation of an ultralow flow interface for coupling capillary electrophoresis (CE) and mass spectrometry (MS), in combination with reversed-phase high-pressure liquid chromatography (HPLC) fractionation as alternate workflow quantitative proteomics. Proteins, extracted from a SILAC (stable isotope labeling by amino acids cell culture) labeled unlabeled yeast strain were mixed digested enzymatically solution. The resulting peptides fractionated using RP-HPLC...