d-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders.
AuthorsXu M, Liu K, Swaroop M, Porter FD, Sidhu R, Finkes S, Ory DS, Marugan JJ, Xiao J, Southall N, Pavan WJ, Davidson C, Walkley SU, Remaley AT, Baxa U, Sun W, McKew JC, Austin CP, Zheng W,
JournalJ Biol Chem
PubMed ID23035117
'Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins. Deficiency in function of either the NPC1 or NPC2 protein in NPC disease or lysosomal acid lipase in Wolman disease results in defective cellular cholesterol ... More
Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways.
AuthorsGarland AL, Walton WG, Coakley RD, Tan CD, Gilmore RC, Hobbs CA, Tripathy A, Clunes LA, Bencharit S, Stutts MJ, Betts L, Redinbo MR, Tarran R,
Journal
PubMed ID24043776
'The ability to maintain proper airway surface liquid (ASL) volume homeostasis is vital for mucus hydration and clearance, which are essential aspects of the mammalian lung''s innate defense system. In cystic fibrosis (CF), one of the most common life-threatening genetic disorders, ASL dehydration leads to mucus accumulation and chronic infection. ... More
Increased acid stability of the hemagglutinin protein enhances H5N1 influenza virus growth in the upper respiratory tract but is insufficient for transmission in ferrets.
Influenza virus entry is mediated by the acidic-pH-induced activation of hemagglutinin (HA) protein. Here, we investigated how a decrease in the HA activation pH (an increase in acid stability) influences the properties of highly pathogenic H5N1 influenza virus in mammalian hosts. We generated isogenic A/Vietnam/1203/2004 (H5N1) (VN1203) viruses containing either ... More
Host cell autophagy modulates early stages of adenovirus infections in airway epithelial cells.
AuthorsZeng X, Carlin CR,
JournalJ Virol
PubMed ID23236070
Human adenoviruses typically cause mild infections in the upper or lower respiratory tract, gastrointestinal tract, or ocular epithelium. However, adenoviruses may be life-threatening in patients with impaired immunity and some serotypes cause epidemic outbreaks. Attachment to host cell receptors activates cell signaling and virus uptake by endocytosis. At present, it ... More
Single-stranded DNA oligonucleotides inhibit TLR3-mediated responses in human monocyte-derived dendritic cells and in vivo in cynomolgus macaques.
AuthorsSköld AE, Hasan M, Vargas L, Saidi H, Bosquet N, Le Grand R, Smith CI, Spetz AL,
JournalBlood
PubMed ID22700721
TLR3 is a key receptor for recognition of double-stranded RNA and initiation of immune responses against viral infections. However, hyperactive responses can have adverse effects, such as virus-induced asthma. Strategies to prevent TLR3-mediated pathology are therefore desired. We investigated the effect of single-stranded DNA oligonucleotides (ssDNA-ODNs) on TLR3 activation. Human ... More
Fatty acids suppress autophagic turnover in ß-cells.
Recent studies have shown that autophagy is essential for proper ß-cell function and survival. However, it is yet unclear under what pathogenic conditions autophagy is inhibited in ß-cells. Here, we report that long term exposure to fatty acids and glucose block autophagic flux in ß-cells, contributing to their toxic effect. ... More
Properties of ribbon and non-ribbon release from rod photoreceptors revealed by visualizing individual synaptic vesicles.
AuthorsChen M, Van Hook MJ, Zenisek D, Thoreson WB,
JournalJ Neurosci
PubMed ID23365244
Vesicle release from rod photoreceptors is regulated by Ca(2+) entry through L-type channels located near synaptic ribbons. We characterized sites and kinetics of vesicle release in salamander rods by using total internal reflection fluorescence microscopy to visualize fusion of individual synaptic vesicles. A small number of vesicles were loaded by ... More
Intracellular vesicle trafficking plays an essential role in mitochondrial quality control.
AuthorsGerards M, Cannino G, de Cózar JMG, Jacobs HT
JournalMol Biol Cell
PubMed ID29343549
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Endophilin B2 facilitates endosome maturation in response to growth factor stimulation, autophagy induction, and influenza A virus infection.
AuthorsSerfass JM, Takahashi Y, Zhou Z, Kawasawa YI, Liu Y, Tsotakos N, Young MM, Tang Z, Yang L, Atkinson JM, Chroneos ZC, Wang HG
JournalJ Biol Chem
PubMed ID28455444
'Endocytosis, and the subsequent trafficking of endosomes, requires dynamic physical alterations in membrane shape that are mediated in part by endophilin proteins. The endophilin B family of proteins contains an N-terminal Bin/amphiphysin/Rvs (N-BAR) domain that induces membrane curvature to regulate intracellular membrane dynamics. Whereas endophilin B1 (SH3GLB1/Bif-1) is known to ... More
MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration.
Authors
JournalMol Neurodegener
PubMed ID34838071
Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate.
Authors
JournalCell Stem Cell
PubMed ID33217323
Dual-functional peptide with defective interfering genes effectively protects mice against avian and seasonal influenza.
Authors
JournalNat Commun
PubMed ID29907765
BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy.
Authors
JournalProc Natl Acad Sci U S A
PubMed ID25991860
A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2.
Authors
JournalNat Commun
PubMed ID32843628
PIP2 depletion and altered endocytosis caused by expression of Alzheimer's disease-protective variant PLCγ2 R522.
Authors
JournalEMBO J
PubMed ID34254352
Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2.
Authors
JournalNat Commun
PubMed ID33750821
LRRK2 and Rab10 coordinate macropinocytosis to mediate immunological responses in phagocytes.
AuthorsDelpiano L, Thomas JJ, Yates AR, Rice SJ, Gray MA, Saint-Criq V
JournalFront Pharmacol
PubMed ID30618754
Respiratory failure, driven by airways mucus obstruction, chronic inflammation and bacterial infections, is the main cause of mortality and morbidity in people with cystic fibrosis (CF) due to defects in the Cl ... More
Quantification of Live Bacterial Sensing for Chemotaxis and Phagocytosis and of Macropinocytosis.
AuthorsMeena NP, Kimmel AR
JournalFront Cell Infect Microbiol
PubMed ID29552545
Initial immunological defense mechanisms to pathogen invasion rely on innate pathways of chemotaxis and phagocytosis, original to ancient phagocytes. Although chemotaxis has been well-studied in mammalian and model systems using purified chemoattractants in defined conditions, directed movement toward live bacteria has been more difficult to assess. ... More