A5084806589- Legionella and Acanthamoeba research
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Vibrio bacteria research studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Erythrocyte Function and Pathophysiology
- Bacterial Genetics and Biotechnology
- Mitochondrial Function and Pathology
- Computational Drug Discovery Methods
- Neonatal Health and Biochemistry
- RNA and protein synthesis mechanisms
- Caveolin-1 and cellular processes
- CRISPR and Genetic Engineering
- Nuclear Structure and Function
- Bacterial biofilms and quorum sensing
- Lipid Membrane Structure and Behavior
- Photosynthetic Processes and Mechanisms
- Trace Elements in Health
- Biomedical Research and Pathophysiology
- Genetics, Aging, and Longevity in Model Organisms
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Cell death mechanisms and regulation
- Signaling Pathways in Disease
University of California, San Francisco
2015-2024
San Francisco Foundation
2017-2024
Chan Zuckerberg Initiative (United States)
2022-2024
Quantitative BioSciences
2020
Yale University
2009-2014
Laboratoire d'Enzymologie et Biochimie Structurales
2013
Centre National de la Recherche Scientifique
2013
Albert Einstein College of Medicine
2002-2011
Yeshiva University
2011
Institut thématique Génétique, génomique et bioinformatique
2010
ABSTRACT An outbreak of the novel coronavirus SARS-CoV-2, causative agent COVID-19 respiratory disease, has infected over 290,000 people since end 2019, killed 12,000, and caused worldwide social economic disruption 1,2 . There are currently no antiviral drugs with proven efficacy nor there vaccines for its prevention. Unfortunately, scientific community little knowledge molecular details SARS-CoV-2 infection. To illuminate this, we cloned, tagged expressed 26 29 viral proteins in human...
In mammalian cells, the Golgi apparatus undergoes extensive fragmentation during apoptosis. p115 is a key vesicle tethering protein required for maintaining structural organization of apparatus. Here, we demonstrate that was cleaved apoptosis by caspases 3 and 8. Compared with control cells expressing native p115, those cleavage-resistant form delayed Expression cDNAs encoding full-length or an NH2-terminal caspase cleavage fragment had no effect on morphology. contrast, expression...
Tethering proteins play a key role in vesicular transport, ensuring that cargo arrives at specific destination. The bacterial effector protein SidC and its paralog SdcA have been described as tethering factors encoded by the intracellular pathogen Legionella pneumophila. Here, we demonstrate are important for early events unique to maturation of vacuoles containing discover monoubiquitination Rab1 new SidC-dependent activity. crystal structure N-terminus revealed novel fold is function could...
The Golgi apparatus undergoes irreversible fragmentation during apoptosis, in part as a result of caspase‐mediated cleavage several Golgi‐associated proteins. However, structure and orientation is also regulated by the cytoskeleton cytoskeletal changes have been implicated inducing apoptosis. Consequently, we analyzed role actin filaments microtubules apoptotic fragmentation. We demonstrate that Fas receptor‐activated cells, was an early event coincided with release cytochrome c from...
Abstract The intracellular pathogen, Legionella pneumophila , secretes ∼300 effector proteins to modulate the host environment. Given intimate interaction between L. and endoplasmic reticulum, we investigated role of unfolded protein response (UPR) during infection. Interestingly, show that identifies infection as a form reticulum stress sensor pATF6 is processed generate pATF6(N), transcriptional activator downstream UPR genes. However, able suppress block translation prototypical genes,...
Glucose transporter 4 (GLUT4) is sequestered inside muscle and fat then released by vesicle traffic to the cell surface in response postprandial insulin for blood glucose clearance. Here, we map biogenesis of this GLUT4 pathway humans, which involves clathrin isoform CHC22. We observe that transits through early secretory more slowly than constitutively secreted GLUT1 localize CHC22 ER-to-Golgi intermediate compartment (ERGIC). functions transport from ERGIC, as demonstrated an essential...
Significance Rab GTPases regulate vesicle traffic within the cell by switching between active (GTP-bound) and inactive (GDP-bound) states. The switch II region of proteins undergoes a significant conformational change to Rab1 is hijacked during intracellular Legionella pneumophila infection bacterial effector-mediated posttranslational modifications region, unique mechanism for regulation function. We present new evidence that endogenously modified TGF-β activated kinase 1 (TAK1), crucial...
Cells adapt to cold by increasing levels of unsaturated phospholipids and membrane fluidity through conserved homeostatic mechanisms. Here we report an exceptionally large evolutionarily protein LPD-3 in C. elegans that mediates lipid trafficking confer resilience. We identify lpd-3 mutants a mutagenesis screen for genetic suppressors the desaturase FAT-7. bridges endoplasmic reticulum (ER) plasma membranes (PM), forming structurally predicted hydrophobic tunnel trafficking. exhibit abnormal...
The Golgi apparatus is a network of polarized cisternae localized to the perinuclear region in mammalian cells. It undergoes extensive vesiculation at onset mitosis and its reassembly requires factors that are part segregated via mitotic spindle. Here we show unlike typical markers, Golgi-protein p115 partitioned with spindle poles throughout mitosis. An armadillo-fold N terminus mediated novel interaction between γ-tubulin functioned centrosomal targeting. Both N- C-terminal regions were...
Eukaryotic initiation factor 6 (eIF6), a highly conserved protein from yeast to mammals, is essential for 60 S ribosome biogenesis and assembly. Both mammalian eIF6 are phosphorylated at Ser-174 Ser-175 by the nuclear isoform of casein kinase 1 (CK1). The molecular basis phosphorylation, however, remains elusive. In present work, we show that subcellular distribution in nuclei cytoplasm cells mediated dephosphorylation respectively. This nucleo-cytoplasmic shuttling dependent on...
During apoptosis the Golgi apparatus undergoes irreversible fragmentation. In part, this results from caspase-mediated cleavage of several high molecular weight coiled-coil proteins, termed golgins. These include GM130, golgin 160, and vesicle tethering protein p115, whose caspase generates a C-terminal fragment (CTF) 205 residues. Here we demonstrate that early during apoptosis, following rapid endogenous CTF translocated to cell nucleus its nuclear import was required enhance apoptotic...
The KEAP1-NFE2L2 axis is essential for the cellular response against metabolic and oxidative stress. KEAP1 an adaptor protein of CUL3 (cullin 3) ubiquitin ligase that controls levels NFE2L2, a critical transcription factor several cytoprotective genes. Oxidative stress, defective autophagy pathogenic infections activate NFE2L2 signaling through phosphorylation receptor SQSTM1, which competes with binding to KEAP1. Here we show phosphoribosyl-linked serine ubiquitination SQSTM1 catalyzed by...
The intracellular bacterial pathogen Legionella pneumophila ( L.p. ) secretes ∼330 effector proteins into the host cell to sculpt an ER-derived replicative niche. We previously reported five effectors that inhibit IRE1, a key sensor of homeostatic unfolded protein response (UPR) pathway. In this study, we discovered subset toxins selectively activate UPR ATF6, resulting in its cleavage, nuclear translocation, and target gene transcription. deviation from conventional model, L.p .–dependent...
The intracellular bacterial pathogen
Abstract Pathogens often secrete proteins or nucleic acids that mimic the structure and/or function of molecules expressed in their hosts. Molecular mimicry empowers pathogens to subvert critical host processes and establish infection. We report intracellular bacterium Legionella pneumophila secretes toxin SidI (substrate icm/dot transporter I), which possesses a transfer RNA (tRNA)-like shape functions as mannosyl transferase. The 3.1 Å cryo-EM reveals an N-terminal domain exhibits...