U.S. Department of Health and Human Services

Laboratory of Cell and Molecular Biology

John A. Hanover, Ph.D., Chief

​Research Images

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The Hexosamine Signaling PathwayThis image depicts the Nutrient Sensing Hexosamine signaling pathway terminating in O-GlcNAc addition and removal. This pathway may be deregulated in human diseases such as diabetes.Enlarge
Calmodulin-Dependent Nuclear ImportEnlarge
OGT isoforms are differentially targeted to nucleus and mitochondria in Hela cellsUsing an antisera to OGT (green) and mitotracker (red), OGT isoforms were shown to be present in nucleus and mitochondria.Enlarge
Structure of the TPR domain of OGT has similarities to Importin alphaEnlarge
O-GlcNAc cycling modulates insulin signaling and Dauer in C. elegansIn C. elegans, insulin-like signaling regulates longevity, stress response, and the entry into the diapause state termed dauer. Knockout of ogt-1 leads to reduced dauer formation (insulin hypersensitivity), while knockout of oga-1 results in enhanced dauer formation (insulin resistance).Enlarge
Hexosamine Signaling and TaopathyThe expression of mutated human tau (V337M) in C. elegans causes a severe uncoordinated motion (unc) phenotype associated with neuronal cell death. When this mutation is crossed to ogt-1(ok430), this phenotype is largely corrected.Enlarge
Ran and CalmodulinEnlarge
The interaction of the CTD of the T4 transcriptional activator MotA with DNAThe interaction of the CTD of the T4 transcriptional activator MotA with DNA is shown using 3-D printed models. The position of the protein on the DNA was determined by conjugating specic residues within MotA with the chemical cleaving reagent FeBABE (Hsieh et al. 2013 J. Biol. Chem. 288: 27607-18). Some of the conjugated residues within MotACTD (E105 [red], E112 [brown], E132 [yellow], E143 [orange]) are shown along with their respective cut sites within the DNA. The double-stranded DNA is from positions -14 to -41 relative to the start site of transcription (+1). The top (non-template) strand is in black; the bottom (template) strand is in gray.Enlarge
Nuclei of wild type and spo7∆ cellsWild type budding yeast cells (left panel) typically have round nuclei containing chromosomes (in blue) and a crescent shaped nucleolus (in green). In contrast, spo7∆ mutant cells (right panel) have a nuclear protrusion at the site of the nucleolus.Enlarge
A model for how the constant nuclear/cell volume can affect nuclear shapeIn yeast, and possibly other cells, there is a constant ratio between nuclear and cell volume. If nuclear surface area increases the nucleus could expand, increasing its volume or the nuclear envelope could form protrusions and invaginations. We propose that the latter happens to maintain a constant nuclear/cell volume ratio.Enlarge
Possible mechanisms of nonvesicular lipid exchange between membranesA,B spontaneously exchange lipid between membranes without proteins. C–G depicts a lipid exchange facilitated by proteins.Enlarge
Reconstruction of DeltaPRD dynamin in the constricted state reveals new structural features of the assembled dynamin polymerTwo density thresholds of the DeltaPRD map are shown: the lower threshold is colored gray, and the higher threshold is in mesh and colored radially to denote the locations of the PH domain (yellow), Middle/GED (blue), and GTPase (green) regions. The top left panel shows a cross-section through PRD polymer; it depicts the classical ‘‘T view’’ of dynamin subunits within individual helical rungs. The top right panel shows a surface view of the GTPase domains (green, labeled Head) and an inner view of the Middle/GED region (blue). The bottom left panel is an end-on view of the tube looking down the helical axis, and the bottom right panel is a side view of the helical assembly. (see Chappie et al., 2012)Enlarge
Docked dynamin tetramers reveal mechanism of constrictionThis image depicts the assembly of long dynamin tetramer models within the GMPPCP-stabilized constricted PRD map (gray). The numbering and rainbow coloring (red to blue) denote the sequential addition of tetramers, and terminates when the first G domain dimer is formed. The left panel depicts a top view of the long assembly looking down the helical axis; the right panel is a side view perpendicular to this axis. The sequential rungs of the dynamin helix are marked in the lower panel with black brackets and numbered as ‘‘1’’ and ‘‘2.’’ The dashed black box highlights the partnering helical rungs facilitating G domain dimerization. (see Chappie et al., 2012)Enlarge
Dnm1 constricts the underlying lipid bilayer upon addition of GTPAs shown on the left, the Dnm1 assembles onto liposomes to form large protein-lipid tubes with a diameter of ~130 nm. Upon GTP addition, the tubes constrict to ~60 nm, as shown in the right panel. Enlarge
SIRT1 is involved in FMR1 gene silencing in Fragile X mental retardation syndromeThis image depicts an artistic representation of events occurring during the silencing of the FMR1 gene in Fragile X mental retardation syndrome (FXS). FXS alleles become associated with SIRT1, which deacetylates histone H3 and histone H4—leading to chromatin compaction and gene silencing. Image Credit: PLoS Genetics, March 2008, Dr. Marian L. Miller (Journal-Cover-Art.com).Enlarge
Fragile X premutation mice show neurodegeneration similar to humans with Fragile X-associated tremor and ataxia syndromeSimilar neurodegeneration includes: (i) Ubiquitin staining [thalamus] (Inset: section [reticular formation] counterstained with Neutral Red), (ii) Lamin-positive inclusions (arrows) and irregular distribution of lamin [cerebellum] (Inset: normal lamin distribution), and (iii-v) Calbindin staining [cerebellum] showing swollen axons, abnormal calbindin distribution, and purkinje cell dropout.Enlarge
Chromosome fragility in FXS cellsIn situ hybridization of metaphase chromosome spreads from a patient with Fragile X syndrome showing the chromosomes in blue and the region of the X chromosome containing the FMR1 gene in yellow.Enlarge