A5085078308- Cellular transport and secretion
- Hippo pathway signaling and YAP/TAZ
- Lipid Membrane Structure and Behavior
- Antibiotic Resistance in Bacteria
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Amino Acid Enzymes and Metabolism
- Venomous Animal Envenomation and Studies
- Immune Response and Inflammation
- Antimicrobial Peptides and Activities
- Cardiac electrophysiology and arrhythmias
- Drug Transport and Resistance Mechanisms
- Bacterial Genetics and Biotechnology
- Microtubule and mitosis dynamics
- Ion Transport and Channel Regulation
- Electrowetting and Microfluidic Technologies
- Lysosomal Storage Disorders Research
- Photoreceptor and optogenetics research
- Insect and Arachnid Ecology and Behavior
- Nicotinic Acetylcholine Receptors Study
- Electrochemical Analysis and Applications
- Protein Kinase Regulation and GTPase Signaling
- Electrohydrodynamics and Fluid Dynamics
- Mitochondrial Function and Pathology
Roche (Switzerland)
2022-2024
The University of Queensland
2014-2021
Consejo Superior de Investigaciones Científicas
2014
How activation leads to gating Voltage-gated sodium (Na v ) channels are key players in electrical signaling. Central their function is fast inactivation, and mutants that impede this cause conditions such as epilepsy pain syndromes. The have four voltage-sensing domains (VSDs), with VSD4 playing an important role inactivation. Clairfeuille et al. determined the structures of a chimera which cockroach channel Na PaS replaced from human 1.7, both apo state bound scorpion toxin impedes (see...
Abstract Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a major global pathogen with limited treatment options 1 . No new antibiotic chemical class activity against A. reached patients in over 50 years Here we report the identification and optimization of tethered macrocyclic peptide (MCP) antibiotics potent antibacterial CRAB. The mechanism action this molecule involves blocking transport bacterial lipopolysaccharide from inner membrane to its destination on outer...
Abstract Gram-negative bacteria are extraordinarily difficult to kill because their cytoplasmic membrane is surrounded by an outer that blocks the entry of most antibiotics. The impenetrable nature due presence a large, amphipathic glycolipid called lipopolysaccharide (LPS) in its leaflet 1 . Assembly requires transport LPS across protein bridge spans from cell surface. Maintaining integrity essential for bacterial viability, and disruption can increase susceptibility other antibiotics 2–6...
Significance Cell surface proteins are regulated by a constant cycle of internalization and recycling from intracellular compartments called endosomes. From these organelles, two protein sorting platforms, nexin 27 (SNX27) the retromer complex, play critical role in retrieval various responsible for ion transport, glucose metabolism, neurotransmission, other cell functions. Based on three-dimensional structure SNX27 complex with subunit VPS26, we define mechanism which cooperate to drive...
The parathyroid hormone 1 receptor (PTHR) is central to the process of bone formation and remodeling. PTHR signaling requires internalization into endosomes, which then terminated by recycling or degradation. Here we show that sorting nexin 27 (SNX27) functions as an adaptor couples retromer trafficking complex. SNX27 binds directly C-terminal PDZ-binding motif PTHR, wiring it for endosomal sorting. structure bound reveals a high-affinity interface involving conserved electrostatic...
The retromer complex acts as a scaffold for endosomal protein complexes that sort integral membrane proteins to various cellular destinations. is heterotrimer of VPS29, VPS35, and VPS26. Two these paralogues, VPS26A VPS26B, are expressed in humans. Retromer dysfunction associated with neurodegenerative disease, recently, three mutations (p.K93E, p.M112V, p.K297X) were discovered be atypical parkinsonism. Here, we apply quantitative proteomics provide detailed description the interactome. By...
Alanine-, serine-, cysteine-preferring transporter 2 (ASCT2, SLC1A5) is responsible for the uptake of glutamine into cells, a major source cellular energy and key regulator mammalian target rapamycin (mTOR) activation. Furthermore, ASCT2 expression has been reported in several human cancers, making it potential both diagnostic therapeutic purposes. Here we identify as membrane-trafficked cargo molecule, sorted through direct interaction with PDZ domain sorting nexin 27 (SNX27). Using...
Sorting nexin 27 (SNX27) controls the endosomal to cell-surface recycling of diverse transmembrane protein cargos. Critical this function is recruitment SNX27 endosomes through binding phosphatidylinositol-3-phosphate (PtdIns3P) by phox-homology (PX) domain. In T cells, polarized immunological synapse (IS) in an activation-dependent manner, but molecular mechanisms underlying translocation remain be clarified. Here, we examined phosphoinositide lipid-binding capabilities full-length SNX27,...
Sorting nexins (SNX) orchestrate membrane trafficking and signaling events required for the proper distribution of proteins within endosomal network. Their phox homology (PX) domain acts as a phosphoinositide (PI) recognition module that targets them to specific endocytic domains. The modularity SNX confers wide variety functions from deformation cargo binding, many SNXs are crucial modulators endosome dynamics involved in myriad physiological pathological processes such neurodegenerative...
The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through of integral proteins the synaptic surface, most notably AMPA receptors. To provide a broader view SNX27-associated pathologies, we performed proteomics in rat primary neurons identify SNX27-dependent cargoes, and identified excitotoxicity, epilepsy, intellectual disabilities, working memory deficits. Focusing on adhesion molecule LRFN2, established that SNX27 binds LRFN2 regulates its...
A microfluidic sample preparation method for TEM, which entirely avoids paper blotting and allows the passivation of air–water interface during process, is presented.
Abstract The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through of integral proteins the synaptic surface, most notably AMPA receptors. To provide a broader view SNX27-associated pathologies we have performed unbiased proteomics identify new neuronal SNX27-dependent cargoes, and identified excitotoxicity (SLC1A3, SLC4A7, SLC6A11), epilepsy, intellectual disabilities working memory deficits (KCNT2, ADAM22, KIDINS220, LRFN2). Focusing on...