A5029002091- Autophagy in Disease and Therapy
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Calcium signaling and nucleotide metabolism
- Toxoplasma gondii Research Studies
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Lipid Membrane Structure and Behavior
- Adenosine and Purinergic Signaling
- interferon and immune responses
- RNA regulation and disease
- Cytomegalovirus and herpesvirus research
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- Cannabis and Cannabinoid Research
- Lysosomal Storage Disorders Research
- Lipid metabolism and biosynthesis
- Polyamine Metabolism and Applications
- RNA modifications and cancer
- Erythrocyte Function and Pathophysiology
- Mosquito-borne diseases and control
- Neurological Disease Mechanisms and Treatments
- Studies on Chitinases and Chitosanases
- Signaling Pathways in Disease
- CRISPR and Genetic Engineering
Max Perutz Labs
2016-2025
University of Vienna
2016-2025
Vienna Biocenter
2013-2024
Research Network (United States)
2021-2024
Medical University of Vienna
2022-2023
Wienerberger (Czechia)
2022
CeMM Research Center for Molecular Medicine
2022
Austrian Academy of Sciences
2022
Child Trends
2016-2019
Berkeley College
2010-2016
Significance Selective autophagy of damaged mitochondria (mitophagy) requires protein kinases PINK1 and TBK1, ubiquitin ligase Parkin, receptors such as OPTN, driving ubiquitin-labeled into autophagosomes. Because all proteins have been genetically linked to either Parkinson’s disease (PINK1 Parkin) or amyotrophic lateral sclerosis frontotemporal lobar degeneration (TBK1 OPTN), it is great interest understand their physiological functions. By utilizing quantitative proteomics we show that...
Synaptic vesicles loaded with neurotransmitters are exocytosed in a soluble N -ethylmaleimide–sensitive factor attachment protein receptor (SNARE)–dependent manner after presynaptic depolarization induces calcium ion (Ca 2+ ) influx. The Ca sensor required for fast fusion is synaptotagmin-1. activation energy of bilayer-bilayer very high (≈40 k B T ). We found that, response to binding, synaptotagmin-1 could promote SNARE-mediated by lowering this barrier inducing positive curvature target...
The p47 GTPases are essential for interferon-γ-induced cell-autonomous immunity against the protozoan parasite, Toxoplasma gondii, in mice, but mechanism of resistance is poorly understood. We show that GTPases, including IIGP1, accumulate at vacuoles containing T. gondii. accumulation GTP-dependent and requires live parasites. Vacuolar IIGP1 accumulations undergo a maturation-like process accompanied by vesiculation parasitophorous vacuole membrane. This culminates disruption finally...
Article17 January 2018Open Access Source DataTransparent process p62 filaments capture and present ubiquitinated cargos for autophagy Gabriele Zaffagnini Department of Biochemistry Cell Biology, Max F. Perutz Laboratories (MFPL), Vienna Biocenter (VBC), University Vienna, Austria Search more papers by this author Adriana Savova Alberto Danieli Julia Romanov Shirley Tremel Structural Computational Biology Unit, European Molecular Laboratory, Heidelberg, Germany Michael Ebner Thomas Peterbauer...
“Spontaneous” Release Trigger Synaptic vesicle release occurs in different phases that can be tightly coupled to action potentials (synchronous), immediately following (asynchronous), or as stochastic events not triggered by (spontaneous). The protein synaptotagmin is thought act the Ca 2+ sensor synchronous phase, but for other two phases, sensors have been identified. Groffen et al. (p. 1614 , published online 11 February) now show cytoplasmic proteins known Doc2 (double C2 domain) are...
The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but molecular mechanism signaling to core machinery is unclear. Here, we show that disordered residues 326–380 directly interact with C-terminal region (CTR) FIP200. Crystal structure determination shows FIP200 CTR contains a dimeric globular domain designated "Claw" for its shape. interaction mediated positively charged pocket in Claw, enhanced...
The activity of the conserved Atg12-Atg5-Atg16 complex is essential for autophagosome formation. However, little known about its mechanism action during this process. In our study we employed in vitro systems consisting purified proteins and giant unilamellar vesicles (GUVs) or small liposomes to investigate membrane binding by interplay with Atg8 conjugation system. We showed that Atg5 directly binds membranes negatively regulated Atg12 but activated Atg16. Membrane required efficient...
Autophagy is a major pathway for the clearance of harmful material from cytoplasm. During autophagy, cytoplasmic delivered into lysosomal system by organelles called autophagosomes. Autophagosomes form in de novo manner and, course their formation, isolate cargo rest Cargo specificity conferred autophagic receptors that selectively link to autophagosomal membrane decorated with ATG8 family proteins such as LC3B. Here we show human receptor p62/SQSTM-1 employs oligomerization stabilize its...
Autophagosomes form de novo in a manner that is incompletely understood. Particularly enigmatic are autophagy-related protein 9 (Atg9)-containing vesicles required for autophagy machinery assembly but do not supply the bulk of autophagosomal membrane. In this study, we reconstituted autophagosome nucleation using recombinant components from yeast. We found Atg9 proteoliposomes first recruited phosphatidylinositol 3-phosphate kinase complex, followed by Atg21, Atg2-Atg18 lipid transfer and...
Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the endoplasmic reticulum (ER). Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged a major mechanism. However, degree which ER-phagy is employed by other branches ER-quality remains largely elusive. Here, we identify cytosolic protein, C53, that specifically recruited autophagosomes during ER-stress, both plant and mammalian cells. C53 interacts with ATG8 distinct binding...
Abstract The autophagic degradation of misfolded and ubiquitinated proteins is important for cellular homeostasis. In this process, which governed by cargo receptors, are condensed into larger structures subsequently become targets the autophagy machinery. Here we employ in vitro reconstitution cell biology to define roles human receptors p62/SQSTM1, NBR1 TAX1BP1 selective substrates. We show that p62 major driver ubiquitin condensate formation. promotes formation equipping p62-NBR1...
Cargo sequestration is a fundamental step of selective autophagy in which cells generate double-membrane structure termed an "autophagosome" on the surface cargoes. NDP52, TAX1BP1, and p62 bind FIP200, recruits ULK1/2 complex to initiate autophagosome formation How OPTN initiates during remains unknown despite its importance neurodegeneration. Here, we uncover unconventional path PINK1/Parkin mitophagy initiation by that does not begin with FIP200 binding or require kinases. Using...
Chemical modulation of proteins enables a mechanistic understanding biology and represents the foundation most therapeutics. However, despite decades research, 80% human proteome lacks functional ligands. proteomics has advanced fragment-based ligand discovery toward cellular systems, but throughput limitations have stymied scalable identification fragment-protein interactions. We report proteome-wide maps protein-binding propensity for 407 structurally diverse small-molecule fragments....
Growing knowledge of the key molecular components involved in biological processes such as endocytosis, exocytosis, and motility has enabled direct testing proposed mechanistic models by reconstitution. However, current techniques for building increasingly complex cellular structures functions from purified are limited their ability to create conditions that emulate physical biochemical constraints real cells. Here we present an integrated method forming giant unilamellar vesicles with...