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 10 of 65

Publication Record

Connections

Nedd4-2 regulates surface expression and may affect N-glycosylation of hyperpolarization-activated cyclic nucleotide-gated (HCN)-1 channels.
Wilkars W, Wollberg J, Mohr E, Han M, Chetkovich DM, Bähring R, Bender RA
(2014) FASEB J 28: 2177-90
MeSH Terms: Amino Acid Motifs, Animals, Brain, Cell Membrane, Down-Regulation, Electrophysiology, Endosomal Sorting Complexes Required for Transport, Female, Gene Expression Regulation, Glycosylation, HEK293 Cells, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Nedd4 Ubiquitin Protein Ligases, Oocytes, Protein Structure, Tertiary, Rats, Rats, Wistar, Receptors, Cytoplasmic and Nuclear, Ubiquitin-Protein Ligases, Xenopus Proteins, Xenopus laevis
Show Abstract · Added April 2, 2019
HCN channels are important regulators of neuronal excitability. The proper function of these channels is governed by various mechanisms, including post-translational modifications of channel subunits. Here, we provide evidence that ubiquitination via a ubiquitin ligase, neuronal precursor cell expressed developmentally downregulated (Nedd)-4-2, is involved in the regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. We identified a PY motif (L/PPxY), the characteristic binding motif for Nedd4-2 in the C terminus of the HCN1 subunit, and showed that HCN1 and Nedd4-2 interacted both in vivo (rat hippocampus, neocortex, and cerebellum) and in vitro [human embryonic kidney 293 (HEK293) cells], resulting in increased HCN1 ubiquitination. Elimination of the PY motif reduced, but did not abolish, Nedd4-2 binding, which further involved a stretch of ∼100 aa downstream in the HCN1 C terminus. Coexpression of Nedd4-2 and HCN1 drastically reduced the HCN1-mediated h-current amplitude (85-92%) in Xenopus laevis oocytes and reduced surface expression (34%) of HCN1 channels in HEK293 cells, thereby opposing effects of tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b)-(1a-4), an auxiliary subunit that promotes HCN1 surface expression. Regulation may further include N-glycosylation of HCN1 channels, which is significantly enhanced by TRIP8b(1a-4), but may be reduced by Nedd4-2. Taken together, our data indicate that Nedd4-2 plays an important role in the regulation of HCN1 trafficking and may compete with TRIP8b(1a-4) in this process.
0 Communities
1 Members
0 Resources
MeSH Terms
XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling.
Hanson AJ, Wallace HA, Freeman TJ, Beauchamp RD, Lee LA, Lee E
(2012) Mol Cell 45: 619-28
MeSH Terms: Animals, Co-Repressor Proteins, Drosophila, Drosophila Proteins, Embryo, Nonmammalian, HEK293 Cells, Humans, Inhibitor of Apoptosis Proteins, Models, Genetic, RNA Interference, Ubiquitination, Wnt Proteins, Wnt Signaling Pathway, Wnt1 Protein, X-Linked Inhibitor of Apoptosis Protein, Xenopus, Xenopus Proteins
Show Abstract · Added June 14, 2013
A key event in Wnt signaling is conversion of TCF/Lef from a transcriptional repressor to an activator, yet how this switch occurs is not well understood. Here, we report an unanticipated role for X-linked inhibitor of apoptosis (XIAP) in regulating this critical Wnt signaling event that is independent of its antiapoptotic function. We identified DIAP1 as a positive regulator of Wingless signaling in a Drosophila S2 cell-based RNAi screen. XIAP, its vertebrate homolog, is similarly required for Wnt signaling in cultured mammalian cells and in Xenopus embryos, indicating evolutionary conservation of function. Upon Wnt pathway activation, XIAP is recruited to TCF/Lef where it monoubiquitylates Groucho (Gro)/TLE. This modification decreases affinity of Gro/TLE for TCF/Lef. Our data reveal a transcriptional switch involving XIAP-mediated ubiquitylation of Gro/TLE that facilitates its removal from TCF/Lef, thus allowing β-catenin-TCF/Lef complex assembly and initiation of a Wnt-specific transcriptional program.
Copyright © 2012 Elsevier Inc. All rights reserved.
2 Communities
4 Members
0 Resources
17 MeSH Terms
Norepinephrine depletion of antimicrobial peptides from the skin glands of Xenopus laevis.
Gammill WM, Fites JS, Rollins-Smith LA
(2012) Dev Comp Immunol 37: 19-27
MeSH Terms: Adrenergic alpha-Agonists, Animals, Antimicrobial Cationic Peptides, Coloring Agents, Exocrine Glands, Molecular Weight, Norepinephrine, Rosaniline Dyes, Skin, Stress, Physiological, Xenopus Proteins, Xenopus laevis
Show Abstract · Added May 20, 2014
The dermal granular glands of the South African clawed frog, Xenopus laevis, contain antimicrobial peptides (AMPs) that are secreted following local nerve stimulation. These natural antibiotics are active against bacteria and fungi including Batrachochytrium dendrobatidis, a fungal pathogen that causes the skin disease chytridiomycosis. Granular gland secretion can be stimulated in the laboratory by norepinephrine injection. We found that two injections of 80nmol/g norepinephrine were necessary to fully deplete the AMP stores. One injection resulted in the secretion of most of the stored peptides. A second injection, 2 days later, released a small amount of additional AMPs that are not compositionally different from those released by the first injection. A third injection, 4 days after the first, did not result in further AMP release. Mass spectrometry and histology confirmed that glands are depleted after two injections. Periodic acid-Schiff staining indicated that mucus gland secretion was also induced by norepinephrine.
Copyright © 2011 Elsevier Ltd. All rights reserved.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Characterization of a central Ca2+/calmodulin-dependent protein kinase IIalpha/beta binding domain in densin that selectively modulates glutamate receptor subunit phosphorylation.
Jiao Y, Jalan-Sakrikar N, Robison AJ, Baucum AJ, Bass MA, Colbran RJ
(2011) J Biol Chem 286: 24806-18
MeSH Terms: Animals, Calcium, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Calmodulin, Humans, Isoenzymes, Mice, Mutation, Phosphorylation, Protein Structure, Tertiary, Rats, Receptors, AMPA, Receptors, N-Methyl-D-Aspartate, Sialoglycoproteins, Swine, Xenopus Proteins, Xenopus laevis
Show Abstract · Added June 21, 2013
The densin C-terminal domain can target Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) in cells. Although the C-terminal domain selectively binds CaMKIIα in vitro, full-length densin associates with CaMKIIα or CaMKIIβ in brain extracts and in transfected HEK293 cells. This interaction requires a second central CaMKII binding site, the densin-IN domain, and an "open" activated CaMKII conformation caused by Ca(2+)/calmodulin binding, autophosphorylation at Thr-286/287, or mutation of Thr-286/287 to Asp. Mutations in the densin-IN domain (L815E) or in the CaMKIIα/β catalytic domain (I205/206K) disrupt the interaction. The amino acid sequence of the densin-IN domain is similar to the CaMKII inhibitor protein, CaMKIIN, and a CaMKIIN peptide competitively blocks CaMKII binding to densin. CaMKII is inhibited by both CaMKIIN and the densin-IN domain, but the inhibition by densin is substrate-selective. Phosphorylation of a model peptide substrate, syntide-2, or of Ser-831 in AMPA receptor GluA1 subunits is fully inhibited by densin. However, CaMKII phosphorylation of Ser-1303 in NMDA receptor GluN2B subunits is not effectively inhibited by densin in vitro or in intact cells. Thus, densin can target multiple CaMKII isoforms to differentially modulate phosphorylation of physiologically relevant downstream targets.
0 Communities
2 Members
0 Resources
17 MeSH Terms
Rapid differential transport of Nodal and Lefty on sulfated proteoglycan-rich extracellular matrix regulates left-right asymmetry in Xenopus.
Marjoram L, Wright C
(2011) Development 138: 475-85
MeSH Terms: Animals, Blotting, Western, Body Patterning, Embryo, Nonmammalian, Extracellular Matrix, Fluorescent Antibody Technique, Gene Expression Regulation, Developmental, Left-Right Determination Factors, Mesoderm, Nodal Protein, Proteoglycans, Xenopus, Xenopus Proteins
Show Abstract · Added January 20, 2015
The spatiotemporally dynamic distribution of instructive ligands within embryonic tissue, and their feedback antagonists, including inherent stabilities and rates of clearance, are affected by interactions with cell surfaces or extracellular matrix (ECM). Nodal (here, Xnr1 or Nodal1 in Xenopus) and Lefty interact in a cross-regulatory relationship in mesendoderm induction, and are the conserved instructors of left-right (LR) asymmetry in early somitogenesis stage embryos. By expressing Xnr1 and Lefty proproteins that produce mature functional epitope-tagged ligands in vivo, we found that ECM is a principal surface of Nodal and Lefty accumulation. We detected Lefty moving faster than Nodal, with evidence that intact sulfated proteoglycans in the ECM facilitate the remarkable long distance movement of Nodal. We propose that Nodal autoregulation substantially aided by rapid ligand transport underlies the anteriorward shift of Nodal expression in the left LPM (lateral plate mesoderm), and speculate that the higher levels of chondroitin-sulfate proteoglycan (CSPG) in more mature anterior regions provide directional transport cues. Immunodetection and biochemical analysis showed transfer of Lefty from left LPM to right LPM, providing direct evidence that left-side-derived Lefty is a significant influence in ensuring the continued suppression of right-sided expression of Nodal, maintaining unilateral expression of this conserved determinant of asymmetry.
1 Communities
1 Members
0 Resources
13 MeSH Terms
Xenopus Kazrin interacts with ARVCF-catenin, spectrin and p190B RhoGAP, and modulates RhoA activity and epithelial integrity.
Cho K, Vaught TG, Ji H, Gu D, Papasakelariou-Yared C, Horstmann N, Jennings JM, Lee M, Sevilla LM, Kloc M, Reynolds AB, Watt FM, Brennan RG, Kowalczyk AP, McCrea PD
(2010) J Cell Sci 123: 4128-44
MeSH Terms: Animals, Armadillo Domain Proteins, Cadherins, Cell Adhesion Molecules, Cell Line, Epithelial Cells, GTPase-Activating Proteins, Humans, Membrane Proteins, Phosphoproteins, Protein Binding, Protein Structure, Tertiary, Spectrin, Two-Hybrid System Techniques, Xenopus, Xenopus Proteins, rhoA GTP-Binding Protein
Show Abstract · Added March 28, 2014
In common with other p120-catenin subfamily members, Xenopus ARVCF (xARVCF) binds cadherin cytoplasmic domains to enhance cadherin metabolic stability or, when dissociated, modulates Rho-family GTPases. We report here that xARVCF binds and is stabilized by Xenopus KazrinA (xKazrinA), a widely expressed conserved protein that bears little homology to established protein families, and which is known to influence keratinocyte proliferation and differentiation and cytoskeletal activity. Although we found that xKazrinA binds directly to xARVCF, we did not resolve xKazrinA within a larger ternary complex with cadherin, nor did it co-precipitate with core desmosomal components. Instead, screening revealed that xKazrinA binds spectrin, suggesting a potential means by which xKazrinA localizes to cell-cell borders. This was supported by the resolution of a ternary biochemical complex of xARVCF-xKazrinA-xβ2-spectrin and, in vivo, by the finding that ectodermal shedding followed depletion of xKazrin in Xenopus embryos, a phenotype partially rescued with exogenous xARVCF. Cell shedding appeared to be the consequence of RhoA activation, and thereby altered actin organization and cadherin function. Indeed, we also revealed that xKazrinA binds p190B RhoGAP, which was likewise capable of rescuing Kazrin depletion. Finally, xKazrinA was found to associate with δ-catenins and p0071-catenins but not with p120-catenin, suggesting that Kazrin interacts selectively with additional members of the p120-catenin subfamily. Taken together, our study supports the essential role of Kazrin in development, and reveals the biochemical and functional association of KazrinA with ARVCF-catenin, spectrin and p190B RhoGAP.
1 Communities
1 Members
0 Resources
17 MeSH Terms
Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α.
Thorne CA, Hanson AJ, Schneider J, Tahinci E, Orton D, Cselenyi CS, Jernigan KK, Meyers KC, Hang BI, Waterson AG, Kim K, Melancon B, Ghidu VP, Sulikowski GA, LaFleur B, Salic A, Lee LA, Miller DM, Lee E
(2010) Nat Chem Biol 6: 829-36
MeSH Terms: Adaptor Proteins, Signal Transducing, Adenomatous Polyposis Coli, Animals, Axin Protein, Casein Kinase I, Casein Kinase Ialpha, Cell Extracts, Cell Line, Tumor, Cell Proliferation, Colonic Neoplasms, Dose-Response Relationship, Drug, Enzyme Activation, Enzyme Inhibitors, Humans, Intracellular Signaling Peptides and Proteins, Oocytes, Pyrvinium Compounds, Repressor Proteins, Signal Transduction, Wnt Proteins, Xenopus Proteins, Xenopus laevis, beta Catenin
Show Abstract · Added February 3, 2014
Wnt/β-catenin signaling is critically involved in metazoan development, stem cell maintenance and human disease. Using Xenopus laevis egg extract to screen for compounds that both stabilize Axin and promote β-catenin turnover, we identified an FDA-approved drug, pyrvinium, as a potent inhibitor of Wnt signaling (EC(50) of ∼10 nM). We show pyrvinium binds all casein kinase 1 (CK1) family members in vitro at low nanomolar concentrations and pyrvinium selectively potentiates casein kinase 1α (CK1α) kinase activity. CK1α knockdown abrogates the effects of pyrvinium on the Wnt pathway. In addition to its effects on Axin and β-catenin levels, pyrvinium promotes degradation of Pygopus, a Wnt transcriptional component. Pyrvinium treatment of colon cancer cells with mutation of the gene for adenomatous polyposis coli (APC) or β-catenin inhibits both Wnt signaling and proliferation. Our findings reveal allosteric activation of CK1α as an effective mechanism to inhibit Wnt signaling and highlight a new strategy for targeted therapeutics directed against the Wnt pathway.
0 Communities
5 Members
0 Resources
23 MeSH Terms
Cellular retinol binding protein 1 modulates photoreceptor outer segment folding in the isolated eye.
Wang X, Tong Y, Giorgianni F, Beranova-Giorgianni S, Penn JS, Jablonski MM
(2010) Dev Neurobiol 70: 623-35
MeSH Terms: Amino Acid Sequence, Animals, Immunohistochemistry, In Situ Hybridization, Larva, Oligonucleotides, Antisense, Retina, Retinal Photoreceptor Cell Outer Segment, Retinal Pigment Epithelium, Retinol-Binding Proteins, Sequence Homology, Amino Acid, Tretinoin, Vitamin A, Xenopus Proteins, Xenopus laevis
Show Abstract · Added October 9, 2013
In a previous study, we used differential proteomics to identify retinal proteins whose steady-state levels were altered in an experimental system in which photoreceptor outer segments were improperly folded. We determined that the steady-state level of cellular retinol binding protein 1 (CRBP1) was downregulated in eyes lacking organized outer segments. The purpose of this study was to determine if CRBP1 is a plausible candidate for regulating outer segment assembly. We used Morpholinos to directly test the hypothesis that a decreased level of CRBP1 protein was associated with the misfolding of outer segments. Results from these studies indicate that downregulation of CRBP1 protein resulted in aberrant assembly of outer segments. Because CRBP1 plays a dual role in the retina-retinal recycling and generation of retinoic acid-we evaluated both possibilities. Our data demonstrate that outer segment folding was not modified by 11-cis retinal supplementation, suggesting that CRBP1 influences outer segment assembly through a mechanism unrelated to rhodopsin regeneration. In contrast, retinoic acid is required for the proper organization of nascent outer segment membranes. The localization of CRBP1 within Muller cells and the RPE and its demonstrated role in modulating the proper folding of nascent outer segment membranes through retinoic acid further elucidates the role of these cells in directly influencing photoreceptor physiology.
(c) 2010 Wiley Periodicals, Inc.
1 Communities
1 Members
0 Resources
15 MeSH Terms
Checkpoint signaling from a single DNA interstrand crosslink.
Ben-Yehoyada M, Wang LC, Kozekov ID, Rizzo CJ, Gottesman ME, Gautier J
(2009) Mol Cell 35: 704-15
MeSH Terms: Alkylating Agents, Animals, Ataxia Telangiectasia Mutated Proteins, Cell Cycle, Cell Cycle Proteins, Cell Proliferation, Checkpoint Kinase 1, DNA, DNA Damage, DNA Helicases, DNA Repair, DNA Replication, DNA-Directed DNA Polymerase, Fanconi Anemia Complementation Group A Protein, Fanconi Anemia Complementation Group D2 Protein, HeLa Cells, Humans, Nucleic Acid Conformation, Protein Kinases, Protein-Serine-Threonine Kinases, Recombinant Proteins, Replication Origin, Replication Protein A, Signal Transduction, Time Factors, Transfection, Xenopus Proteins, Xenopus laevis
Show Abstract · Added January 7, 2016
DNA interstrand crosslinks (ICLs) are the most toxic lesions induced by chemotherapeutic agents such as mitomycin C and cisplatin. By covalently linking both DNA strands, ICLs prevent DNA melting, transcription, and replication. Studies on ICL signaling and repair have been limited, because these drugs generate additional DNA lesions that trigger checkpoint signaling. Here, we monitor sensing, signaling from, and repairing of a single site-specific ICL in cell-free extract derived from Xenopus eggs and in mammalian cells. Notably, we demonstrate that ICLs trigger a checkpoint response independently of origin-initiated DNA replication and uncoupling of DNA polymerase and DNA helicase. The Fanconi anemia pathway acts upstream of RPA-ATR-Chk1 to generate the ICL signal. The system also repairs ICLs in a reaction that involves extensive, error-free DNA synthesis. Repair occurs by both origin-dependent and origin-independent mechanisms. Our data suggest that cell sensitivity to crosslinking agents results from both checkpoint and DNA repair defects.
0 Communities
1 Members
0 Resources
28 MeSH Terms
DeltaNp63 antagonizes p53 to regulate mesoderm induction in Xenopus laevis.
Barton CE, Tahinci E, Barbieri CE, Johnson KN, Hanson AJ, Jernigan KK, Chen TW, Lee E, Pietenpol JA
(2009) Dev Biol 329: 130-9
MeSH Terms: Activins, Animals, Cell Line, Cell Line, Tumor, Dose-Response Relationship, Drug, Down-Regulation, Embryo, Nonmammalian, Epithelium, Humans, Immunohistochemistry, Keratinocytes, Mesoderm, Models, Biological, Oligonucleotides, Antisense, Organ Culture Techniques, Phosphoproteins, RNA, Small Interfering, Trans-Activators, Transcription Factors, Transfection, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, Xenopus Proteins, Xenopus laevis
Show Abstract · Added March 5, 2014
p63, a homolog of the tumor suppressor p53, is critical for the development and maintenance of complex epithelia. The developmentally regulated p63 isoform, DeltaNp63, can act as a transcriptional repressor, but the link between the transcriptional functions of p63 and its biological roles is unclear. Based on our initial finding that the mesoderm-inducing factor activin A is suppressed by DeltaNp63 in human keratinocytes, we investigated the role of DeltaNp63 in regulating mesoderm induction during early Xenopus laevis development. We find that down-regulation of DeltaNp63 by morpholino injection in the early Xenopus embryo potentiates mesoderm formation whereas ectopic expression of DeltaNp63 inhibits mesoderm formation. Furthermore, we show that mesodermal induction after down-regulation of DeltaNp63 is dependent on p53. We propose that a key function for p63 in defining a squamous epithelial phenotype is to actively suppress mesodermal cell fates during early development. Collectively, we show that there is a distinct requirement for different p53 family members during the development of both mesodermal and ectodermal tissues. These findings have implications for the role of p63 and p53 in both development and tumorigenesis of human epithelia.
0 Communities
2 Members
0 Resources
24 MeSH Terms