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: 11 to 20 of 82

Publication Record

Connections

Interaction of p190RhoGAP with C-terminal domain of p120-catenin modulates endothelial cytoskeleton and permeability.
Zebda N, Tian Y, Tian X, Gawlak G, Higginbotham K, Reynolds AB, Birukova AA, Birukov KG
(2013) J Biol Chem 288: 18290-9
MeSH Terms: Adherens Junctions, Antigens, CD, Binding Sites, Blotting, Western, Cadherins, Catenins, Cell Membrane, Cell Membrane Permeability, Cells, Cultured, Cytoskeleton, Endothelial Cells, Fluorescent Antibody Technique, GTPase-Activating Proteins, Guanine Nucleotide Exchange Factors, HEK293 Cells, Humans, Mutation, Phosphatidylcholines, Protein Binding, Protein Interaction Mapping, Repressor Proteins, Thrombin, p21-Activated Kinases, rac1 GTP-Binding Protein
Show Abstract · Added March 7, 2014
p120-catenin is a multidomain intracellular protein, which mediates a number of cellular functions, including stabilization of cell-cell transmembrane cadherin complexes as well as regulation of actin dynamics associated with barrier function, lamellipodia formation, and cell migration via modulation of the activities of small GTPAses. One mechanism involves p120 catenin interaction with Rho GTPase activating protein (p190RhoGAP), leading to p190RhoGAP recruitment to cell periphery and local inhibition of Rho activity. In this study, we have identified a stretch of 23 amino acids within the C-terminal domain of p120 catenin as the minimal sequence responsible for the recruitment of p190RhoGAP (herein referred to as CRAD; catenin-RhoGAP association domain). Expression of the p120-catenin truncated mutant lacking the CRAD in endothelial cells attenuated effects of barrier protective oxidized phospholipid, OxPAPC. This effect was accompanied by inhibition of membrane translocation of p190RhoGAP, increased Rho signaling, as well as suppressed activation of Rac1 and its cytoskeletal effectors PAK1 (p21-activated kinase 1) and cortactin. Expression of p120 catenin-truncated mutant lacking CRAD also delayed the recovery process after thrombin-induced endothelial barrier disruption. Concomitantly, RhoA activation and downstream signaling were sustained for a longer period of time, whereas Rac signaling was inhibited. These data demonstrate a critical role for p120-catenin (amino acids 820-843) domain in the p120-catenin·p190RhoGAP signaling complex assembly, membrane targeting, and stimulation of p190RhoGAP activity toward inhibition of the Rho pathway and reciprocal up-regulation of Rac signaling critical for endothelial barrier regulation.
1 Communities
1 Members
0 Resources
24 MeSH Terms
N-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways.
Ouyang M, Lu S, Kim T, Chen CE, Seong J, Leckband DE, Wang F, Reynolds AB, Schwartz MA, Wang Y
(2013) Nat Commun 4: 1589
MeSH Terms: Actin Cytoskeleton, Animals, CHO Cells, Cadherins, Catenins, Cell Polarity, Chickens, Cricetinae, Embryo, Mammalian, Fibroblasts, Fluorescent Dyes, Integrins, Intercellular Junctions, Mice, Models, Biological, Phosphatidylinositol 3-Kinases, Protein Binding, RNA, Small Interfering, Rats, Recombinant Fusion Proteins, Signal Transduction, beta Catenin, rac GTP-Binding Proteins
Show Abstract · Added March 28, 2014
The spatial distribution of molecular signals within cells is crucial for cellular functions. Here, as a model to study the polarized spatial distribution of molecular activities, we used cells on micropatterned strips of fibronectin with one end free and the other end contacting a neighbouring cell. Phosphoinositide 3-kinase and the small GTPase Rac display greater activity at the free end, whereas myosin II light chain and actin filaments are enriched near the intercellular junction. Phosphoinositide 3-kinase and Rac polarization depend specifically on the N-cadherin-p120 catenin complex, whereas myosin II light chain and actin filament polarization depend on the N-cadherin-β-catenin complex. Integrins promote high phosphoinositide 3-kinase/Rac activities at the free end, and the N-cadherin-p120 catenin complex excludes integrin α5 at the junctions to suppress local phosphoinositide 3-kinase and Rac activity. We hence conclude that N-cadherin couples with distinct effectors to polarize phosphoinositide 3-kinase/Rac and myosin II light chain/actin filaments in migrating cells.
1 Communities
1 Members
0 Resources
23 MeSH Terms
The Scribble polarity protein stabilizes E-cadherin/p120-catenin binding and blocks retrieval of E-cadherin to the Golgi.
Lohia M, Qin Y, Macara IG
(2012) PLoS One 7: e51130
MeSH Terms: Animals, Cadherins, Catenins, Cell Nucleus, Cell Polarity, Endocytosis, Golgi Apparatus, Humans, Lysosomes, Madin Darby Canine Kidney Cells, Membrane Proteins, Models, Biological, Protein Binding, Protein Stability, Protein Transport, Vesicular Transport Proteins
Show Abstract · Added March 20, 2014
Several polarity proteins, including Scribble (Scrb) have been implicated in control of vesicle traffic, and in particular the endocytosis of E-cadherin, but through unknown mechanisms. We now show that depletion of Scrb enhances endocytosis of E-cadherin by weakening the E-cadherin-p120catenin interaction. Unexpectedly, however, the internalized E-cadherin is not degraded but accumulates in the Golgi apparatus. Silencing p120-catenin causes degradation of E-cadherin in lysosomes, but degradation is blocked by the co-depletion of Scrb, which diverts the internalized E-cadherin to the Golgi. Loss of Scrb also enhances E-cadherin binding to retromer components, and retromer is required for Golgi accumulation of Scrb, and E-cadherin stability. These data identify a novel and unanticipated function for Scrb in blocking retromer-mediated diversion of E-cadherin to the Golgi. They provide evidence that polarity proteins can modify the intracellular itinerary for endocytosed membrane proteins.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Monoclonal antibodies to DIPA: a novel binding partner of p120-catenin isoform 1.
Markham NO, Cooper T, Goff M, Gribben EM, Carnahan RH, Reynolds AB
(2012) Hybridoma (Larchmt) 31: 246-54
MeSH Terms: Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Antibodies, Monoclonal, Murine-Derived, Antibody Specificity, Blotting, Western, Catenins, Cell Line, Dogs, Fluorescent Antibody Technique, Indirect, Gene Knockdown Techniques, Humans, Immunoglobulin G, Immunoprecipitation, Mice, Molecular Sequence Data, Protein Isoforms, RNA Interference, Rats, Repressor Proteins
Show Abstract · Added December 12, 2013
The coiled-coil domain-containing delta-interacting protein A (DIPA) is a transcription factor implicated in developmental regulation. DIPA is the first protein discovered to selectively interact with the p120-catenin (p120) isoform 1, an alternatively spliced form of p120 expressed preferentially in mesenchymal cells. Although a small fraction of p120 can be observed in the nucleus under certain circumstances, the vast majority of it associates with classical cadherins at adherens junctions. We observed for the first time that a discrete fraction of DIPA exists at cell-cell junctions, in addition to its predominantly nuclear localization. Thus, the p120-DIPA interaction may regulate cell signaling and/or transcriptional events, as has been described previously for β-catenin and the LEF/TCF transcription factor family. To facilitate further study of DIPA and to determine the physiological relevance of its interaction with p120, we have generated and characterized a panel of five DIPA-specific monoclonal antibodies (MAbs) that function in immunoblotting, immunoprecipitation, and immunofluorescence assays.
2 Communities
5 Members
1 Resources
20 MeSH Terms
Phosphorylation of Rab11-FIP2 regulates polarity in MDCK cells.
Lapierre LA, Avant KM, Caldwell CM, Oztan A, Apodaca G, Knowles BC, Roland JT, Ducharme NA, Goldenring JR
(2012) Mol Biol Cell 23: 2302-18
MeSH Terms: Adherens Junctions, Animals, Blotting, Western, Cadherins, Catenins, Cell Line, Cell Polarity, Claudins, Dogs, Epithelial Cells, Green Fluorescent Proteins, HEK293 Cells, Humans, Kidney, Membrane Proteins, Microscopy, Confocal, Mutation, Occludin, Phosphorylation, Reverse Transcriptase Polymerase Chain Reaction, Serine, Tight Junctions, Vesicular Transport Proteins
Show Abstract · Added October 7, 2013
The Rab11 effector Rab11-family interacting protein 2 (Rab11-FIP2) regulates transcytosis through its interactions with Rab11a and myosin Vb. Previous studies implicated Rab11-FIP2 in the establishment of polarity in Madin-Darby canine kidney (MDCK) cells through phosphorylation of Ser-227 by MARK2. Here we examine the dynamic role of Rab11-FIP2 phosphorylation on MDCK cell polarity. Endogenous Rab11-FIP2 phosphorylated on Ser-227 coalesces on vesicular plaques during the reestablishment of polarity after either monolayer wounding or calcium switch. Whereas expression of the nonphosphorylatable Rab11-FIP2(S227A) elicits a loss in lumen formation in MDCK cell cysts grown in Matrigel, the putative pseudophosphorylated Rab11-FIP2(S227E) mutant induces the formation of cysts with multiple lumens. On permeable filters, Rab11-FIP2(S227E)-expressing cells exhibit alterations in the composition of both the adherens and tight junctions. At the adherens junction, p120 catenin and K-cadherin are retained, whereas the majority of the E-cadherin is lost. Although ZO-1 is retained at the tight junction, occludin is lost and the claudin composition is altered. Of interest, the effects of Rab11-FIP2 on cellular polarity did not involve myosin Vb or Rab11a. These results indicate that Ser-227 phosphorylation of Rab11-FIP2 regulates the composition of both adherens and tight junctions and is intimately involved in the regulation of polarity in epithelial cells.
1 Communities
3 Members
0 Resources
23 MeSH Terms
A membrane fusion protein αSNAP is a novel regulator of epithelial apical junctions.
Naydenov NG, Brown B, Harris G, Dohn MR, Morales VM, Baranwal S, Reynolds AB, Ivanov AI
(2012) PLoS One 7: e34320
MeSH Terms: Adherens Junctions, Animals, Apoptosis, Catenins, Cattle, Cell Adhesion Molecules, Colon, Down-Regulation, Endoplasmic Reticulum, Epithelial Cells, Golgi Apparatus, Guanine Nucleotide Exchange Factors, Humans, Intercellular Junctions, Permeability, Protein Transport, Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins, Tight Junctions, beta Catenin
Show Abstract · Added March 28, 2014
Tight junctions (TJs) and adherens junctions (AJs) are key determinants of the structure and permeability of epithelial barriers. Although exocytic delivery to the cell surface is crucial for junctional assembly, little is known about the mechanisms controlling TJ and AJ exocytosis. This study was aimed at investigating whether a key mediator of exocytosis, soluble N-ethylmaleimide sensitive factor (NSF) attachment protein alpha (αSNAP), regulates epithelial junctions. αSNAP was enriched at apical junctions in SK-CO15 and T84 colonic epithelial cells and in normal human intestinal mucosa. siRNA-mediated knockdown of αSNAP inhibited AJ/TJ assembly and establishment of the paracellular barrier in SK-CO15 cells, which was accompanied by a significant down-regulation of p120-catenin and E-cadherin expression. A selective depletion of p120 catenin effectively disrupted AJ and TJ structure and compromised the epithelial barrier. However, overexpression of p120 catenin did not rescue the defects of junctional structure and permeability caused by αSNAP knockdown thereby suggesting the involvement of additional mechanisms. Such mechanisms did not depend on NSF functions or induction of cell death, but were associated with disruption of the Golgi complex and down-regulation of a Golgi-associated guanidine nucleotide exchange factor, GBF1. These findings suggest novel roles for αSNAP in promoting the formation of epithelial AJs and TJs by controlling Golgi-dependent expression and trafficking of junctional proteins.
1 Communities
1 Members
0 Resources
19 MeSH Terms
p120-catenin is essential for terminal end bud function and mammary morphogenesis.
Kurley SJ, Bierie B, Carnahan RH, Lobdell NA, Davis MA, Hofmann I, Moses HL, Muller WJ, Reynolds AB
(2012) Development 139: 1754-64
MeSH Terms: Animals, Blotting, Western, Catenins, Cell Line, Cells, Cultured, Female, Gene Expression Regulation, Developmental, Humans, Immunohistochemistry, Mammary Glands, Animal, Mice, Morphogenesis, Wound Healing
Show Abstract · Added February 17, 2014
Although p120-catenin (p120) is crucial for E-cadherin function, ablation experiments in epithelial tissues from different organ systems reveal markedly different effects. Here, we examine for the first time the consequences of p120 knockout during mouse mammary gland development. An MMTV-Cre driver was used to target knockout to the epithelium at the onset of puberty. p120 ablation was detected in approximately one-quarter of the nascent epithelium at the forth week post-partum. However, p120 null cells were essentially nonadherent, excluded from the process of terminal end bud (TEB) morphogenesis and lost altogether by week six. This elimination process caused a delay in TEB outgrowth, after which the gland developed normally from cells that had retained p120. Mechanistic studies in vitro indicate that TEB dysfunction is likely to stem from striking E-cadherin loss, failure of cell-cell adhesion and near total exclusion from the collective migration process. Our findings reveal an essential role for p120 in mammary morphogenesis.
3 Communities
4 Members
0 Resources
13 MeSH Terms
Regulation of cochlear convergent extension by the vertebrate planar cell polarity pathway is dependent on p120-catenin.
Chacon-Heszele MF, Ren D, Reynolds AB, Chi F, Chen P
(2012) Development 139: 968-78
MeSH Terms: Animals, Cadherins, Catenins, Cell Polarity, Cochlea, Hair Cells, Auditory, Mice, Mice, Transgenic, Morphogenesis, Nerve Tissue Proteins, Protein Precursors, Vertebrates
Show Abstract · Added March 28, 2014
The vertebrate planar cell polarity (PCP) pathway consists of conserved PCP and ciliary genes. During development, the PCP pathway regulates convergent extension (CE) and uniform orientation of sensory hair cells in the cochlea. It is not clear how these diverse morphogenetic processes are regulated by a common set of PCP genes. Here, we show that cellular contacts and geometry change drastically and that the dynamic expression of N-cadherin and E-cadherin demarcates sharp boundaries during cochlear extension. The conditional knockout of a component of the adherens junctions, p120-catenin, leads to the reduction of E-cadherin and N-cadherin and to characteristic cochlear CE defects but not misorientation of hair cells. The specific CE defects in p120-catenin mutants are in contrast to associated CE and hair cell misorientation defects observed in common PCP gene mutants. Moreover, the loss-of-function of a conserved PCP gene, Vangl2, alters the dynamic distribution of N-cadherin and E-cadherin in the cochlea and causes similar abnormalities in cellular morphology to those found in p120-catenin mutants. Conversely, we found that Pcdh15 interacts genetically with PCP genes to regulate the formation of polar hair bundles, but not CE defects in the cochlea. Together, these results indicate that the vertebrate PCP pathway regulates CE and hair cell polarity independently and that a p120-catenin-dependent mechanism regulates CE of the cochlea.
2 Communities
1 Members
0 Resources
12 MeSH Terms
Association of Rho-associated protein kinase 1 with E-cadherin complexes is mediated by p120-catenin.
Smith AL, Dohn MR, Brown MV, Reynolds AB
(2012) Mol Biol Cell 23: 99-110
MeSH Terms: Actins, Cadherins, Catenins, Cell Line, Gene Knockdown Techniques, Guanine Nucleotide Exchange Factors, Humans, Intercellular Junctions, Microscopy, Fluorescence, Multiprotein Complexes, Protein Binding, Protein Interaction Mapping, Protein Transport, RNA Interference, Repressor Proteins, rho-Associated Kinases
Show Abstract · Added March 5, 2014
The dynamic functional linkage of cadherins with the underlying actin cytoskeleton is tightly regulated to achieve proper cell-cell adhesion. p120-catenin (p120) regulates both cadherin stability and actin dynamics, but the relationship between these two functions remains unclear. Using a novel proteomic approach called reversible cross-link immunoprecipitation, or ReCLIP, we previously identified a physical interaction between p120 and Rho-associated protein kinase 1 (ROCK1), a major effector of RhoA. In this paper, we show that a discrete fraction of cellular ROCK1 coimmunoprecipitates with p120 and precisely colocalizes to adherens junctions (AJs). Manipulation of AJs using a calcium-switch assay and cadherin-blocking antibodies indicates direct recruitment of ROCK1 to newly forming junctions. Importantly, we find that p120 links ROCK1 to the cadherin complex, as ROCK1 coimmunoprecipitates with wild-type but not p120-uncoupled E-cadherin. Moreover, depletion of ROCK1 using short-hairpin RNA results in dramatic mislocalization of the cadherin complex and junctional actin. These data are consistent with a model in which p120 dynamically regulates Rho-GTPase activity at the cadherin complex through transient interaction with several of its up- and downstream effectors, including ROCK1.
1 Communities
1 Members
0 Resources
16 MeSH Terms
The evolutionary history of the catenin gene family during metazoan evolution.
Zhao ZM, Reynolds AB, Gaucher EA
(2011) BMC Evol Biol 11: 198
MeSH Terms: Animals, Bayes Theorem, Biological Evolution, Catenins, Evolution, Molecular, Gene Duplication, Humans, Phylogeny
Show Abstract · Added March 28, 2014
BACKGROUND - Catenin is a gene family composed of three subfamilies; p120, beta and alpha. Beta and p120 are homologous subfamilies based on sequence and structural comparisons, and are members of the armadillo repeat protein superfamily. Alpha does not appear to be homologous to either beta or p120 based on the lack of sequence and structural similarity, and the alpha subfamily belongs to the vinculin superfamily. Catenins link the transmembrane protein cadherin to the cytoskeleton and thus function in cell-cell adhesion. To date, only the beta subfamily has been evolutionarily analyzed and experimentally studied for its functions in signaling pathways, development and human diseases such as cancer. We present a detailed evolutionary study of the whole catenin family to provide a better understanding of how this family has evolved in metazoans, and by extension, the evolution of cell-cell adhesion.
RESULTS - All three catenin subfamilies have been detected in metazoans used in the present study by searching public databases and applying species-specific BLAST searches. Two monophyletic clades are formed between beta and p120 subfamilies using Bayesian phylogenetic inference. Phylogenetic analyses also reveal an array of duplication events throughout metazoan history. Furthermore, numerous annotation issues for the catenin family have been detected by our computational analyses.
CONCLUSIONS - Delta2/ARVCF catenin in the p120 subfamily, beta catenin in the beta subfamily, and alpha2 catenin in the alpha subfamily are present in all metazoans analyzed. This implies that the last common ancestor of metazoans had these three catenin subfamilies. However, not all members within each subfamily were detected in all metazoan species. Each subfamily has undergone duplications at different levels (species-specific, subphylum-specific or phylum-specific) and to different extents (in the case of the number of homologs). Extensive annotation problems have been resolved in each of the three catenin subfamilies. This resolution provides a more coherent description of catenin evolution.
1 Communities
1 Members
0 Resources
8 MeSH Terms