Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 6 of 6

Publication Record

Connections

mVps34 deletion in podocytes causes glomerulosclerosis by disrupting intracellular vesicle trafficking.
Chen J, Chen MX, Fogo AB, Harris RC, Chen JK
(2013) J Am Soc Nephrol 24: 198-207
MeSH Terms: Animals, Autophagy, Class III Phosphatidylinositol 3-Kinases, Cytoplasmic Vesicles, Female, Gene Deletion, Glomerulosclerosis, Focal Segmental, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Electron, Podocytes, Protein Transport, Proteinuria, TOR Serine-Threonine Kinases
Show Abstract · Added August 19, 2013
Recent studies have suggested that autophagy is a key mechanism in maintaining the integrity of podocytes. The mammalian homologue of yeast vacuolar protein sorting defective 34 (mVps34) has been implicated in the regulation of autophagy, but its role in podocytes is unknown. We generated a line of podocyte-specific mVps34-knockout (mVps34(pdKO)) mice, which were born at Mendelian ratios. These mice appeared grossly normal at 2 weeks of age but exhibited growth retardation and were significantly smaller than control mice by 6 weeks of age, with no difference in ratios of kidney to body weight. mVps34(pdKO) mice developed significant proteinuria by 3 weeks of age, developed severe kidney lesions by 5-6 weeks of age, and died before 9 weeks of age. There was striking podocyte vacuolization and proteinaceous casts, with marked glomerulosclerosis and interstitial fibrosis by 6 weeks of age. Electron microscopy revealed numerous enlarged vacuoles and increased autophagosomes in the podocytes, with complete foot process effacement and irregular and thickened glomerular basement membranes. Immunoblotting of isolated glomerular lysates revealed markedly elevated markers specific for lysosomes (LAMP1 and LAMP2) and autophagosomes (LC3-II/I). Immunofluorescence staining confirmed that the enlarged vacuoles originated from lysosomes. In conclusion, these results demonstrate an indispensable role for mVps34 in the trafficking of intracellular vesicles to protect the normal cellular metabolism, structure, and function of podocytes.
2 Communities
1 Members
0 Resources
16 MeSH Terms
Enterocyte microvillus-derived vesicles detoxify bacterial products and regulate epithelial-microbial interactions.
Shifrin DA, McConnell RE, Nambiar R, Higginbotham JN, Coffey RJ, Tyska MJ
(2012) Curr Biol 22: 627-31
MeSH Terms: Alkaline Phosphatase, Animals, Caco-2 Cells, Cytoplasmic Vesicles, Enterocytes, Enteropathogenic Escherichia coli, Epithelial Cells, Humans, Intestine, Small, Lipopolysaccharides, Microscopy, Electron, Transmission, Microvilli, Myosin Heavy Chains, Myosin Type I, Rats
Show Abstract · Added March 27, 2014
The continuous monolayer of intestinal epithelial cells (IECs) lining the gut lumen functions as the site of nutrient absorption and as a physical barrier to prevent the translocation of microbes and associated toxic compounds into the peripheral vasculature. IECs also express host defense proteins such as intestinal alkaline phosphatase (IAP), which detoxify bacterial products and prevent intestinal inflammation. Our laboratory recently showed that IAP is enriched on vesicles that are released from the tips of IEC microvilli and accumulate in the intestinal lumen. Here, we show that these native "lumenal vesicles" (LVs) (1) contain catalytically active IAP that can dephosphorylate lipopolysaccharide (LPS), (2) cluster on the surface of native lumenal bacteria, (3) prevent the adherence of enteropathogenic E. coli (EPEC) to epithelial monolayers, and (4) limit bacterial population growth. We also find that IECs upregulate LV production in response to EPEC and other Gram-negative pathogens. Together, these results suggest that microvillar vesicle shedding represents a novel mechanism for distributing host defense machinery into the intestinal lumen and that microvillus-derived LVs modulate epithelial-microbial interactions.
Copyright © 2012 Elsevier Ltd. All rights reserved.
2 Communities
2 Members
0 Resources
15 MeSH Terms
The C/EBPbeta isoform, liver-inhibitory protein (LIP), induces autophagy in breast cancer cell lines.
Abreu MM, Sealy L
(2010) Exp Cell Res 316: 3227-38
MeSH Terms: Acids, Apoptosis, Autophagy, Breast Neoplasms, CCAAT-Enhancer-Binding Protein-beta, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Cytoplasmic Vesicles, Female, Humans, Microtubule-Associated Proteins, Necrosis, Protein Isoforms, Vacuoles
Show Abstract · Added May 20, 2014
Autophagy is a process involving the bulk degradation of cellular components in the cytoplasm via the lysosomal degradation pathway. Autophagy manifests a protective role in stressful conditions such as nutrient or growth factor depletion; however, extensive degradation of regulatory molecules or organelles essential for survival can lead to the demise of the cell, or autophagy-mediated cell death. The role of autophagy in cancer is complex with roles in both tumor suppression and tumor promotion proposed. Here we report that an isoform of the C/EBPbeta transcription factor, liver-enriched inhibitory protein (LIP), induces cell death in human breast cancer cells and stimulates autophagy. Overexpression of LIP is incompatible with cell growth and when cell cycle analysis was performed, a DNA profile of cells undergoing apoptosis was not observed. Instead, LIP expressing cells appeared to have large autophagic vesicles when examined via electron microscopy. Autophagy was further assessed in LIP expressing cells by monitoring the development of acidic vesicular organelles and conversion of LC3 from the cytoplasmic form to the membrane-bound form. Our work shows that C/EBPbeta isoform, LIP, is another member of the group of transcription factors, including E2F1 and p53, which are capable of playing a role in autophagy.
Copyright © 2010 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
15 MeSH Terms
A differential role for endocytosis in receptor-mediated activation of Nox1.
Miller FJ, Chu X, Stanic B, Tian X, Sharma RV, Davisson RL, Lamb FS
(2010) Antioxid Redox Signal 12: 583-93
MeSH Terms: Activating Transcription Factor 1, Animals, Cells, Cultured, Cytoplasmic Vesicles, Dynamins, Endocytosis, Endosomes, Enzyme Activation, Humans, Isoenzymes, Membrane Microdomains, Mice, Mice, Inbred C57BL, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, NADPH Oxidases, Oxidation-Reduction, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Reactive Oxygen Species, Signal Transduction, Thrombin, Tumor Necrosis Factor-alpha
Show Abstract · Added February 22, 2016
Internalization of activated receptors to a compartment enriched with NAPDH oxidase and associated signaling molecules is expected to facilitate regulation of redox-mediated signal transduction. The aim of this study was to test the hypothesis that endocytosis is necessary for generation of reactive oxygen species (ROS) by Nox1 and for redox-dependent signaling in smooth muscle cells (SMCs). Within minutes of treatment with tumor necrosis factor (TNF)-alpha or thrombin, SMCs increased cellular levels of ROS that was inhibited by shRNA to Nox1. Treatment of SMC with TNF-alpha induced a dynamin-dependent endosomal generation of ROS, whereas thrombin-mediated ROS production did not occur within endosomes and was not prevented by dominant-negative dynamin (dn-dynamin), but instead required transactivation of the epidermal growth factor receptor (EGFR). Activation of the phosphatidylinositol 3-kinase (PI3K)-Akt-activating transcription factor-1 (ATF-1) pathway by TNF-alpha and thrombin were both Nox1- and dynamin-dependent. In conclusion, we show that formation of specific ligand-receptor complexes results in spatially distinct mechanisms of Nox1 activation and generation of ROS. These findings provide novel insights into the role of compartmentalization for integrating redox-dependent cell signaling.
0 Communities
1 Members
0 Resources
23 MeSH Terms
Dyggve-Melchior-Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic.
Osipovich AB, Jennings JL, Lin Q, Link AJ, Ruley HE
(2008) Proc Natl Acad Sci U S A 105: 16171-6
MeSH Terms: Animals, Biological Transport, Cells, Cultured, Chondrodysplasia Punctata, Cytoplasmic Vesicles, Humans, Membrane Proteins, Mice, Mutation, Protein Binding, Syndrome
Show Abstract · Added April 18, 2013
Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia are recessive spondyloepimetaphyseal dysplasias caused by loss-of-function mutations in dymeclin (Dym), a gene with previously unknown function. Here we report that Dym-deficient mice display defects in endochondral bone formation similar to that of Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia, demonstrating functional conservation between the two species. Dym-mutant cells display multiple defects in vesicle traffic, as evidenced by enhanced dispersal of Golgi markers in interphase cells, delayed Golgi reassembly after brefeldin A treatment, delayed retrograde traffic of an endoplasmic reticulum-targeted Shiga toxin B subunit, and altered furin trafficking; and the Dym protein associates with multiple cellular proteins involved in vesicular traffic. These results establish dymeclin as a novel protein involved in Golgi organization and intracellular vesicle traffic and clarify the molecular basis for chondrodysplasia in mice and men.
0 Communities
3 Members
0 Resources
11 MeSH Terms
The Ran GTPase cycle is required for yeast nuclear pore complex assembly.
Ryan KJ, McCaffery JM, Wente SR
(2003) J Cell Biol 160: 1041-53
MeSH Terms: Alleles, Cycloheximide, Cytoplasmic Vesicles, Genes, Fungal, Green Fluorescent Proteins, Luminescent Proteins, Membrane Proteins, Mutation, Nuclear Envelope, Nuclear Pore, Nuclear Pore Complex Proteins, Protein Synthesis Inhibitors, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Temperature, ran GTP-Binding Protein
Show Abstract · Added March 21, 2014
Here, we report the first evidence that the Ran GTPase cycle is required for nuclear pore complex (NPC) assembly. Using a genetic approach, factors required for NPC assembly were identified in Saccharomyces cerevisiae. Four mutant complementation groups were characterized that correspond to respective mutations in genes encoding Ran (gsp1), and essential Ran regulatory factors Ran GTPase-activating protein (rna1), Ran guanine nucleotide exchange factor (prp20), and the RanGDP import factor (ntf2). All the mutants showed temperature-dependent mislocalization of green fluorescence protein (GFP)-tagged nucleoporins (nups) and the pore-membrane protein Pom152. A decrease in GFP fluorescence associated with the nuclear envelope was observed along with an increase in the diffuse, cytoplasmic signal with GFP foci. The defects did not affect the stability of existing NPCs, and nup mislocalization was dependent on de novo protein synthesis and continued cell growth. Electron microscopy analysis revealed striking membrane perturbations and the accumulation of vesicles in arrested mutants. Using both biochemical fractionation and immunoelectron microscopy methods, these vesicles were shown to contain nups. We propose a model wherein a Ran-mediated vesicular fusion step is required for NPC assembly into intact nuclear envelopes.
0 Communities
1 Members
0 Resources
17 MeSH Terms