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Cell Biology Commons

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2014

Cells

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Articles 1 - 12 of 12

Full-Text Articles in Cell Biology

Structure-Based Network Analysis Of Activation Mechanisms In The Erbb Family Of Receptor Tyrosine Kinases: The Regulatory Spine Residues Are Global Mediators Of Structural Stability And Allosteric Interactions, Kevin A. James, Gennady M. Verkhivker Nov 2014

Structure-Based Network Analysis Of Activation Mechanisms In The Erbb Family Of Receptor Tyrosine Kinases: The Regulatory Spine Residues Are Global Mediators Of Structural Stability And Allosteric Interactions, Kevin A. James, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced ‘‘superacceptor’’ activity ...


Regulated Splicing Of The Alpha6 Integrin Cytoplasmic Domain Determines The Fate Of Breast Cancer Stem Cells, Hira Lal Goel, Tatiana Gritsko, Bryan Pursell, Cheng Chang, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Leslie M. Shaw, Arthur M. Mercurio Nov 2014

Regulated Splicing Of The Alpha6 Integrin Cytoplasmic Domain Determines The Fate Of Breast Cancer Stem Cells, Hira Lal Goel, Tatiana Gritsko, Bryan Pursell, Cheng Chang, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

Although the alpha6beta1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 is tightly controlled and occurs as ...


Human Breast Progenitor Cell Numbers Are Regulated By Wnt And Tbx3, Lisa M. Arendt, Jessica St. Laurent, Ania Wronski, Silvia Caballero, Stephen Lyle, Stephen P. Naber, Charlotte Kuperwasser Oct 2014

Human Breast Progenitor Cell Numbers Are Regulated By Wnt And Tbx3, Lisa M. Arendt, Jessica St. Laurent, Ania Wronski, Silvia Caballero, Stephen Lyle, Stephen P. Naber, Charlotte Kuperwasser

Open Access Articles

BACKGROUND: Although human breast development is mediated by hormonal and non-hormonal means, the mechanisms that regulate breast progenitor cell activity remain to be clarified. This limited understanding of breast progenitor cells has been due in part to the lack of appropriate model systems to detect and characterize their properties.

METHODS: To examine the effects of WNT signaling and TBX3 expression on progenitor activity in the breast, primary human mammary epithelial cells (MEC) were isolated from reduction mammoplasty tissues and transduced with lentivirus to overexpress WNT1 or TBX3 or reduce expression of their cognate receptors using shRNA. Changes in progenitor activity ...


Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis In Drosophila, Alla Amcheslavsky, Wei Song, Qi Li, Yingchao Nie, Ivan Bragatto, Dominique Ferrandon, Norbert Perrimon, Y. Tony Ip Oct 2014

Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis In Drosophila, Alla Amcheslavsky, Wei Song, Qi Li, Yingchao Nie, Ivan Bragatto, Dominique Ferrandon, Norbert Perrimon, Y. Tony Ip

UMass Center for Clinical and Translational Science Supported Publications

Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains unclear. We show here that newly eclosed scute loss-of-function mutant flies are completely devoid of enteroendocrine cells. These enteroendocrine cell-less flies have normal ingestion and fecundity but shorter lifespan. Moreover, in these newly eclosed mutant flies, the diet-stimulated midgut growth that depends on the insulin-like peptide 3 expression in the surrounding muscle is defective. The depletion of Tachykinin-producing ...


Tlr Sorting By Rab11 Endosomes Maintains Intestinal Epithelial-Microbial Homeostasis, Shiyan Yu, Yingchao Nie, Y. Tony Ip, Nan Gao Sep 2014

Tlr Sorting By Rab11 Endosomes Maintains Intestinal Epithelial-Microbial Homeostasis, Shiyan Yu, Yingchao Nie, Y. Tony Ip, Nan Gao

UMass Center for Clinical and Translational Science Supported Publications

Compartmentalization of Toll-like receptors (TLRs) in intestinal epithelial cells (IECs) regulates distinct immune responses to microbes; however, the specific cellular machinery that controls this mechanism has not been fully identified. Here we provide genetic evidences that the recycling endosomal compartment in enterocytes maintains a homeostatic TLR9 intracellular distribution, supporting mucosal tolerance to normal microbiota. Genetic ablation of a recycling endosome resident small GTPase, Rab11a, a gene adjacent to a Crohn's disease risk locus, in mouse IECs and in Drosophila midgut caused epithelial cell-intrinsic cytokine production, inflammatory bowel phenotype, and early mortality. Unlike wild-type controls, germ-free Rab11a-deficient mouse intestines failed ...


Evaluation Of The Contribution Of Multiple Damps And Damp Receptors In Cell Death-Induced Sterile Inflammatory Responses, Hiroshi Kataoka, Hajime Kono, Zubin Patel, Kenneth L. Rock Aug 2014

Evaluation Of The Contribution Of Multiple Damps And Damp Receptors In Cell Death-Induced Sterile Inflammatory Responses, Hiroshi Kataoka, Hajime Kono, Zubin Patel, Kenneth L. Rock

Open Access Articles

When cells die by necrosis in vivo they stimulate an inflammatory response. It is thought that this response is triggered when the injured cells expose proinflammatory molecules, collectively referred to as damage associated molecular patterns (DAMPs), which are recognized by cells or soluble molecules of the innate or adaptive immune system. Several putative DAMPs and/or their receptors have been identified, but whether and how much they participate in responses in vivo is incompletely understood, and they have not previously been compared side-by-side in the same models. This study focuses on evaluating the contribution of multiple mechanisms that have been ...


A System For Genome-Wide Histone Variant Dynamics In Es Cells Reveals Dynamic Macroh2a2 Replacement At Promoters, Ozlem Yildirim, Jui-Hung Hung, Ryan J. Cedeno, Zhiping Weng, Christopher J. Lengner, Oliver J. Rando Aug 2014

A System For Genome-Wide Histone Variant Dynamics In Es Cells Reveals Dynamic Macroh2a2 Replacement At Promoters, Ozlem Yildirim, Jui-Hung Hung, Ryan J. Cedeno, Zhiping Weng, Christopher J. Lengner, Oliver J. Rando

Open Access Articles

Dynamic exchange of a subset of nucleosomes in vivo plays important roles in epigenetic inheritance of chromatin states, chromatin insulator function, chromosome folding, and the maintenance of the pluripotent state of embryonic stem cells. Here, we extend a pulse-chase strategy for carrying out genome-wide measurements of histone dynamics to several histone variants in murine embryonic stem cells and somatic tissues, recapitulating expected characteristics of the well characterized H3.3 histone variant. We extended this system to the less-studied MacroH2A2 variant, commonly described as a "repressive" histone variant whose accumulation in chromatin is thought to fix the epigenetic state of differentiated ...


Cooperative Binding Of The Outer Arm-Docking Complex Underlies The Regular Arrangement Of Outer Arm Dynein In The Axoneme, Mikito Owa, Akane Furuta, Jiro Usukura, Fumio Arisaka, Stephen M. King, George B. Witman, Ritsu Kamiya, Ken-Ichi Wakabayashi Jul 2014

Cooperative Binding Of The Outer Arm-Docking Complex Underlies The Regular Arrangement Of Outer Arm Dynein In The Axoneme, Mikito Owa, Akane Furuta, Jiro Usukura, Fumio Arisaka, Stephen M. King, George B. Witman, Ritsu Kamiya, Ken-Ichi Wakabayashi

Cell and Developmental Biology Publications

Outer arm dynein (OAD) in cilia and flagella is bound to the outer doublet microtubules every 24 nm. Periodic binding of OADs at specific sites is important for efficient cilia/flagella beating; however, the molecular mechanism that specifies OAD arrangement remains elusive. Studies using the green alga Chlamydomonas reinhardtii have shown that the OAD-docking complex (ODA-DC), a heterotrimeric complex present at the OAD base, functions as the OAD docking site on the doublet. We find that the ODA-DC has an ellipsoidal shape approximately 24 nm in length. In mutant axonemes that lack OAD but retain the ODA-DC, ODA-DC molecules are ...


Gene Expression Profiling Identifies The Zinc-Finger Protein Charlatan As A Regulator Of Intestinal Stem Cells In Drosophila, Alla Amcheslavsky, Yingchao Nie, Qi Li, Feng He, Leo Tsuda, Michele Markstein, Y. Tony Ip Jul 2014

Gene Expression Profiling Identifies The Zinc-Finger Protein Charlatan As A Regulator Of Intestinal Stem Cells In Drosophila, Alla Amcheslavsky, Yingchao Nie, Qi Li, Feng He, Leo Tsuda, Michele Markstein, Y. Tony Ip

UMass Center for Clinical and Translational Science Supported Publications

Intestinal stem cells (ISCs) in the adult Drosophila midgut can respond to tissue damage and support repair. We used genetic manipulation to increase the number of ISC-like cells in the adult midgut and performed gene expression profiling to identify potential ISC regulators. A detailed analysis of one of these potential regulators, the zinc-finger protein Charlatan, was carried out. MARCM clonal analysis and RNAi in precursor cells showed that loss of Chn function caused severe ISC division defects, including loss of EdU incorporation, phosphorylated histone 3 staining and expression of the mitotic protein Cdc2. Loss of Charlatan also led to a ...


Regulated Splicing Of The Alpha6 Integrin Cytoplasmic Domain Determines The Fate Of Breast Cancer Stem Cells, Hira Lal Goel, Tatiana Gritsko, Bryan Pursell, Cheng Chang, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Leslie M. Shaw, Arthur M. Mercurio May 2014

Regulated Splicing Of The Alpha6 Integrin Cytoplasmic Domain Determines The Fate Of Breast Cancer Stem Cells, Hira Lal Goel, Tatiana Gritsko, Bryan Pursell, Cheng Chang, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Leslie M. Shaw, Arthur M. Mercurio

Cancer Biology Publications and Presentations

Although the alpha6beta1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 is tightly controlled and occurs as ...


Angiomotins Link F-Actin Architecture To Hippo Pathway Signaling, Sebastian Mana-Capelli, Murugan Paramasivam, Shubham Dutta, Dannel Mccollum May 2014

Angiomotins Link F-Actin Architecture To Hippo Pathway Signaling, Sebastian Mana-Capelli, Murugan Paramasivam, Shubham Dutta, Dannel Mccollum

GSBS Student Publications

The Hippo pathway regulates the transcriptional coactivator YAP to control cell proliferation, organ size, and stem cell maintenance. Multiple factors, such as substrate stiffness, cell density, and G protein-coupled receptor signaling, regulate YAP through their effects on the F-actin cytoskeleton, although the mechanism is not known. Here we show that angiomotin proteins (AMOT130, AMOTL1, and AMOTL2) connect F-actin architecture to YAP regulation. First, we show that angiomotins are required to relocalize YAP to the cytoplasm in response to various manipulations that perturb the actin cytoskeleton. Second, angiomotins associate with F-actin through a conserved F-actin-binding domain, and mutants defective for F-actin ...


Mnk2 Alternative Splicing Modulates The P38-Mapk Pathway And Impacts Ras-Induced Transformation, Avraham Maimon, Maxim Mogilevsky, Asaf Shilo, Regina Golan-Gerstl, Akram Obiedat, Vered Ben-Hur, Ilana Lebenthal-Loinger, Ilan Stein, Reuven Reich, Jonah Beenstock, Eldar Zehorai, Claus L. Andersen, Kasper Thorsen, Torben F. Orntoft, Roger J. Davis, Ben Davidson, David Mu, Rotem Karni Apr 2014

Mnk2 Alternative Splicing Modulates The P38-Mapk Pathway And Impacts Ras-Induced Transformation, Avraham Maimon, Maxim Mogilevsky, Asaf Shilo, Regina Golan-Gerstl, Akram Obiedat, Vered Ben-Hur, Ilana Lebenthal-Loinger, Ilan Stein, Reuven Reich, Jonah Beenstock, Eldar Zehorai, Claus L. Andersen, Kasper Thorsen, Torben F. Orntoft, Roger J. Davis, Ben Davidson, David Mu, Rotem Karni

Davis Lab Publications

The kinase Mnk2 is a substrate of the MAPK pathway and phosphorylates the translation initiation factor eIF4E. In humans, MKNK2, the gene encoding for Mnk2, is alternatively spliced yielding two splicing isoforms with differing last exons: Mnk2a, which contains a MAPK-binding domain, and Mnk2b, which lacks it. We found that the Mnk2a isoform is downregulated in breast, lung, and colon tumors and is tumor suppressive. Mnk2a directly interacts with, phosphorylates, activates, and translocates p38alpha-MAPK into the nucleus, leading to activation of its target genes, increasing cell death and suppression of Ras-induced transformation. Alternatively, Mnk2b is pro-oncogenic and does not activate ...