A5028894572- Cellular transport and secretion
- HIV Research and Treatment
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Mosquito-borne diseases and control
- Calcium signaling and nucleotide metabolism
- Virus-based gene therapy research
- Lysosomal Storage Disorders Research
- Retinal Development and Disorders
- Nuclear Structure and Function
- Genetic and Kidney Cyst Diseases
- Chemokine receptors and signaling
- Erythrocyte Function and Pathophysiology
- Phagocytosis and Immune Regulation
- Renal and related cancers
- Biomedical Research and Pathophysiology
- Pancreatic function and diabetes
- Lipid Membrane Structure and Behavior
- Biosensors and Analytical Detection
- SARS-CoV-2 detection and testing
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Protist diversity and phylogeny
- Renal Diseases and Glomerulopathies
King's College London
2012-2023
King's College School
2007-2015
Guy's Hospital
2007-2015
St Thomas' Hospital
2007
Rockefeller University
2003-2005
Aaron Diamond AIDS Research Center
2001-2005
Infectious Disease Consultants
2005
Research Institute Hospital 12 de Octubre
1998-2001
Hospital Universitario 12 De Octubre
1998
During cytokinesis, as dividing animal cells pull apart into two daughter cells, the final stage, termed abscission, requires breakage of midbody, a thin membranous stalk connecting cells. This membrane fission event topologically resembles budding viruses, such HIV-1, from infected We found that proteins involved in HIV-1 budding-tumor susceptibility gene 101 (Tsg101), subunit endosomal sorting complex required for transport I (ESCRT-I), and Alix, an ESCRT-associated protein-were recruited...
The release of enveloped viruses from infected cells often requires a virally encoded activity, termed late-budding domain (L domain), by essential PTAP, PPXY, or YPDL sequence motifs. PTAP-type L domains recruit one three endosomal sorting complexes required for transport (ESCRT-I). However, subsequent events in viral budding are poorly defined, and neither nor PPXY-type require ESCRT-I. Here, we show that ESCRT-I other class E vacuolar protein (VPS) factors linked complex series...
To Cut or Not to During animal cell division, the final separation of daughter cells requires ESCRT-III (endosomal sorting complex required for transport III), core membrane scission machinery. Carlton et al. (p. 220 , published online 15 March; see Perspective by Petronczki and Uhlmann ) report that modulates abscission timing through one its subunits, CHMP4C. Depletion CHMP4C results in faster resolution midbody, cytoplasmic bridge connects at end cytokinesis. This phenotype correlates...
Retroviral late-budding (L) domains are required for the efficient release of nascent virions. The three known types L domain, designated according to essential tetrapeptide motifs (PTAP, PPXY, or YPDL), each bind distinct cellular cofactors. We and others have demonstrated that recruitment an ESCRT-I subunit, Tsg101, a component class E vacuolar protein sorting (VPS) machinery, is budding viruses, such as human immunodeficiency virus type 1 (HIV-1) Ebola virus, encode PTAP-type but...
The ESCRT machinery functions in topologically equivalent membrane fission events, namely multivesicular body formation, the terminal stages of cytokinesis and HIV-1 release. Here, we show that ESCRT-III-binding protein Alix is recruited to midbody dividing cells through binding Cep55 via an evolutionarily conserved peptide. Disruption Cep55/Alix/ESCRT-III interactions causes formation aberrant midbodies cytokinetic failure, demonstrating essential role for these proteins morphology cell...
Many enveloped viruses exploit the class E vacuolar protein-sorting (VPS) pathway to bud from cells, and use peptide motifs recruit specific VPS factors. Homologous E6AP COOH terminus (HECT) ubiquitin ligases have been implicated as cofactors for PPXY motif–dependent budding, but precisely which members of this family are responsible, how they access is unclear. Here, we show that PPXY-dependent viral budding unusually sensitive inhibitory fragments derived HECT ligases, namely WWP1 WWP2. We...
Since the initial discovery of endosomal sorting complex required for transport (ESCRT) pathway, research in this field has exploded. ESCRT proteins are part trafficking system and play a crucial role biogenesis multivesicular bodies by functioning formation vesicles that bud away from cytoplasm. Subsequently, surprising was defined budding step some enveloped retroviruses, including HIV-1. also employed outward process, which results resolution membranous tether between host cell virus...
The last steps of multivesicular body (MVB) formation, human immunodeficiency virus (HIV)-1 budding and cytokinesis require a functional endosomal sorting complex required for transport (ESCRT) machinery to facilitate topologically equivalent membrane fission events. Increased sodium tolerance (IST) 1, new positive modulator the ESCRT pathway, has been described recently, but an essential function this highly conserved protein not identified. Here, we describe previously uncharacterized...
The endosomal sorting complexes required for transport (ESCRT) machinery mediates the physical separation between daughter cells during cytokinetic abscission. This process is regulated by abscission checkpoint, a genome protection mechanism that relies on Aurora B and ESCRT-III subunit CHMP4C to delay in response chromosome missegregation. In this study, we show Unc-51-like kinase 3 (ULK3) phosphorylates binds subunits via tandem MIT domains, thereby, delays lagging chromosomes, nuclear...
Many enveloped viruses encode late assembly domains, or L that facilitate virion egress. PTAP-type domains act by recruiting the ESCRT-I (endosomal sorting complex required for transport I) component Tsg101, and YPXL/LXXLF-type recruit AIP-1/ALIX, both of which are class E vacuolar protein (VPS) factors, normally generation vesicles within endosomes. The binding cofactors PPXY-type have not been unambiguously resolved but may include Nedd4-like ubiquitin ligases. Largely because they as...
Late domains are short peptide sequences encoded by enveloped viruses to promote the final separation of nascent virus from infected cell. These amino acid motifs facilitate viral egress interacting with components ESCRT (endosomal sorting complex required for transport) machinery, ultimately leading membrane scission recruiting ESCRT-III site budding. PPXY late (L) present in such as murine leukemia (MLV) or human T-cell type 1 (HTLV-1) access pathway via interaction HECT ubiquitin ligases...
The “class E” vacuolar protein sorting (VPS) pathway mediates of ubiquitinated cargo into the forming vesicles multivesicular bodies (MVB), and it is essential for down-regulation signaling by growth factors budding enveloped viruses such as Ebola HIV-1. Work in yeast has identified DOA4 a gene that recruited class E machinery to remove ubiquitin from endosomal before incorporated MVB vesicles, but identity mammalian counterpart unclear. Here we report interaction AMSH (associated molecule...
The endosomal sorting complexes required for transport (ESCRTs) facilitate of ubiquitinated cargo, MVB biogenesis, late stages cytokinesis, and retroviral budding. Here we show that ubiquitin associated protein 1 (UBAP1), a subunit human ESCRT-I, coassembles in stable 1:1:1:1 complex with Vps23/TSG101, VPS28, VPS37. X-ray crystal structure the C-terminal region UBAP1 reveals domain describe as solenoid overlapping UBAs (SOUBA). NMR analysis shows each three rigidly arranged making up SOUBA...
Abstract Neural circuits are refined by both functional and structural changes. Structural remodeling large-scale pruning occurs where relatively long neuronal branches cut away from their parent neuron removed local degeneration. Until now, the molecular mechanisms executing such branch severing events have remained poorly understood. Here, we reveal a role for Endosomal Sorting Complex Required Transport (ESCRT) machinery during remodeling. Our data show that specific ESCRT module,...
The coordinated reformation of the nuclear envelope (NE) after mitosis re-establishes structural integrity and functionality compartment. endosomal sorting complex required for transport (ESCRT) machinery, a membrane remodeling pathway that is highly conserved in eukaryotes, has been recently involved NE resealing by mediating annular fusion (NM). We show here CC2D1B, regulator ESCRT polymerization, to re-establish compartmentalization coordinating endoplasmic reticulum (ER) deposition...
Cytokinetic abscission facilitates the irreversible separation of daughter cells. This process requires endosomal-sorting complexes required for transport (ESCRT) machinery and is tightly regulated by charged multivesicular body protein 4C (CHMP4C), an ESCRT-III subunit that engages checkpoint (NoCut) in response to mitotic problems such as persisting chromatin bridges within midbody. Importantly, a human polymorphism CHMP4C (rs35094336, CHMP4CT232) increases cancer susceptibility. Here, we...
There is a worldwide need for reagents to perform SARS-CoV-2 detection. Some laboratories have implemented kit-free protocols, but many others do not the capacity develop these and/or manual processing. We provide multiple workflows nucleic acid detection in clinical samples by comparing several commercially available RNA extraction methods: QIAamp Viral Mini Kit (QIAgen), RNAdvance Blood/Viral (Beckman) and Mag-Bind DNA/RNA 96 (Omega Bio-tek). also compared One-step RT-qPCR reagents: TaqMan...