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The transport of cargo in eukaryotic cells is mediated by the movement of membranous vesicles that pinch off from one membrane and fuse with another. An essential part of this process is the interaction between SNARE 1 (soluble NSF attachment protein receptors) proteins from the vesicle (v-SNARE) and target (t-SNARE) membranes. The resulting SNARE complexes(More)
In Na-reabsorbing tight epithelia, the rate-limiting step for Na transport is the highly selective low-conductance amiloride-sensitive epithelial Na channel (type 1 ENaC). In rat distal colon, type 1 ENaC is made of three homologous subunits. The aim of this study was to identify the corresponding genes of the renal channel from the kidney-derived A6 cell(More)
The small G protein K-Ras2A is rapidly induced by aldosterone in A6 epithelia. In these Xenopus sodium reabsorbing cells, aldosterone rapidly activates preexisting epithelial Na+ channels (XENaC) via a transcriptionally mediated mechanism. In the Xenopus oocytes expression system, we tested whether the K-Ras2A pathway impacts on XENaC activity by expressing(More)
High-throughput single-cell transcriptomics offers an unbiased approach for understanding the extent, basis and function of gene expression variation between seemingly identical cells. Here we sequence single-cell RNA-seq libraries prepared from over 1,700 primary mouse bone-marrow-derived dendritic cells spanning several experimental conditions. We find(More)
Large-scale surveys of single-cell gene expression have the potential to reveal rare cell populations and lineage relationships but require efficient methods for cell capture and mRNA sequencing. Although cellular barcoding strategies allow parallel sequencing of single cells at ultra-low depths, the limitations of shallow sequencing have not been(More)
p97 (also called VCP), a member of the AAA ATPase family, is involved in several cellular processes, including membrane fusion and extraction of proteins from the endoplasmic reticulum for cytoplasmic degradation. We have studied the conformational changes that p97 undergoes during the ATPase cycle by cryo-EM and single-particle analysis. Three-dimensional(More)
Evolution of minimal DNA tumor virus' genomes has selected for small viral oncoproteins that hijack critical cellular protein interaction networks. The structural basis for the multiple and dominant functions of adenovirus oncoproteins has remained elusive. E4-ORF3 forms a nuclear polymer and simultaneously inactivates p53, PML, TRIM24, and MRE11/RAD50/NBS1(More)
SNARE proteins are required for intracellular membrane fusion. In the neuron, the plasma membrane SNAREs syntaxin 1a and SNAP25 bind to VAMP2 found on neurotransmitter-containing vesicles. These three proteins contain "SNARE regions" that mediate their association into stable tetrameric coiled-coil structures. Syntaxin 1a contributes one such region,(More)
Cancer genome sequencing studies have identified numerous driver genes, but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently mutated genes and(More)
DNA topoisomerases manage chromosome supercoiling and organization in all forms of life. Gyrase, a prokaryotic heterotetrameric type IIA topo, introduces negative supercoils into DNA by an ATP-dependent strand passage mechanism. All gyrase orthologs rely on a homologous set of catalytic domains for function; however, these enzymes also can possess(More)