scholarly journals Gene Families With Stochastic Exclusive Gene Choice Underlie Cell Adhesion in Mammalian Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Mikhail Iakovlev ◽  
Simone Faravelli ◽  
Attila Becskei
Keyword(s):  
Cell Adhesion ◽  
Mammalian Cells ◽  
Gene Families ◽  
Cell Types ◽  
Cell Receptor ◽  
Mean Value ◽  
Odorant Receptors ◽  
Receptor Isoforms ◽  
Multiple Cell ◽  
Large Repertoire

Exclusive stochastic gene choice combines precision with diversity. This regulation enables most T-cells to express exactly one T-cell receptor isoform chosen from a large repertoire, and to react precisely against diverse antigens. Some cells express two receptor isoforms, revealing the stochastic nature of this process. A similar regulation of odorant receptors and protocadherins enable cells to recognize odors and confer individuality to cells in neuronal interaction networks, respectively. We explored whether genes in other families are expressed exclusively by analyzing single-cell RNA-seq data with a simple metric. This metric can detect exclusivity independently of the mean value and the monoallelic nature of gene expression. Chromosomal segments and gene families are more likely to express genes concurrently than exclusively, possibly due to the evolutionary and biophysical aspects of shared regulation. Nonetheless, gene families with exclusive gene choice were detected in multiple cell types, most of them are membrane proteins involved in ion transport and cell adhesion, suggesting the coordination of these two functions. Thus, stochastic exclusive expression extends beyond the prototypical families, permitting precision in gene choice to be combined with the diversity of intercellular interactions.

scholarly journals Gene families with stochastic exclusive gene choice underlie cell adhesion in mammalian cells

2020 ◽  
Author(s):  
Mikhail Iakovlev ◽  
Simone Faravelli ◽  
Attila Becskei
Keyword(s):  
Cell Adhesion ◽  
Mammalian Cells ◽  
Gene Families ◽  
Cell Types ◽  
Cell Receptor ◽  
Odorant Receptors ◽  
Rna Seq ◽  
Receptor Isoforms ◽  
Multiple Cell ◽  
Large Repertoire

ABSTRACTExclusive stochastic gene choice combines precision with diversity. This regulation enables most T-cells to express exactly one T-cell receptor isoform chosen from a large repertoire, and to react precisely against diverse antigens. Some cells express two receptor isoforms, revealing the stochastic nature of this process. A similar regulation of odorant receptors and protocadherins enable cells to recognize odors and confer individuality to cells in neuronal interaction networks, respectively. We explored whether genes in other families are expressed exclusively by analyzing single cell RNA-seq data with a simple metric. Chromosomal segments and families are more likely to express genes concurrently than exclusively, possibly due to the evolutionary and biophysical aspects of shared regulation. Nonetheless, gene families with exclusive gene choice were detected in multiple cell types, most of them are membrane proteins involved in ion transport and cell adhesion, suggesting the coordination of these two functions. Thus, stochastic exclusive expression extends beyond the prototypical families, permitting precision in gene choice to be combined with the diversity of intercellular interactions.

scholarly journals Multiparametric analysis of focal adhesion formation by RNAi-mediated gene knockdown

2009 ◽  
Vol 186 (3) ◽  
pp. 423-436 ◽  
Author(s):  
Sabina E. Winograd-Katz ◽  
Shalev Itzkovitz ◽  
Zvi Kam ◽  
Benjamin Geiger
Keyword(s):  
Cell Adhesion ◽  
Adhesion Formation ◽  
Focal Adhesions ◽  
Gene Families ◽  
Adaptor Proteins ◽  
Small Interfering Rnas ◽  
Comprehensive Information ◽  
Focal Adhesion Formation ◽  
Multiple Cell ◽  
And Migration

Cell adhesion to the extracellular matrix is mediated by elaborate networks of multiprotein complexes consisting of adhesion receptors, cytoskeletal components, signaling molecules, and diverse adaptor proteins. To explore how specific molecular pathways function in the assembly of focal adhesions (FAs), we performed a high-throughput, high-resolution, microscopy-based screen. We used small interfering RNAs (siRNAs) to target human kinases, phosphatases, and migration- and adhesion-related genes. Multiparametric image analysis of control and of siRNA-treated cells revealed major correlations between distinct morphological FA features. Clustering analysis identified different gene families whose perturbation induced similar effects, some of which uncoupled the interfeature correlations. Based on these findings, we propose a model for the molecular hierarchy of FA formation, and tested its validity by dynamic analysis of FA formation and turnover. This study provides a comprehensive information resource on the molecular regulation of multiple cell adhesion features, and sheds light on signaling mechanisms regulating the formation of integrin adhesions.

scholarly journals xbx-4, a homolog of the Joubert syndrome gene FAM149B1, acts via the CCRK and MAK kinase cascade to regulate cilia morphology

2021 ◽  
Author(s):  
Ashish K Maurya ◽  
Piali Sengupta
Keyword(s):  
Sensory Neuron ◽  
Mammalian Cells ◽  
Primary Cilia ◽  
Cell Types ◽  
Joubert Syndrome ◽  
C Elegans ◽  
Kinase Cascade ◽  
Multiple Cell ◽  
Kinase Pathway ◽  
Sensory Functions

Primary cilia are microtubule (MT)-based organelles that mediate sensory functions in multiple cell types. Disruption of cilia structure or function leads to a diverse collection of diseases termed ciliopathies. Mutations in the DUF3719 domain-containing protein FAM149B1 have recently been shown to elongate cilia via unknown mechanisms and result in the ciliopathy Joubert syndrome. The highly conserved CCRK and MAK/RCK kinases negatively regulate cilia length and structure in Chlamydomonas, C. elegans, and mammalian cells. How the activity of this kinase cascade is tuned to precisely regulate cilia architecture is unclear. Here we identify XBX-4, a DUF3719 domain-containing protein related to human FAM149B1, as a novel regulator of the DYF-18 CCRK and DYF-5 MAK kinase pathway in C. elegans. As in dyf-18 and dyf-5 mutants, sensory neuron cilia are elongated in xbx-4 mutants and exhibit altered axonemal MT stability. XBX-4 promotes DYF-18 CCRK activity to regulate DYF-5 MAK function and localization. We find that Joubert syndrome-associated mutations in the XBX-4 DUF3719 domain also elongate cilia in C. elegans. Our results identify a new metazoan-specific regulator of this highly conserved kinase pathway, and suggest that FAM149B1 may similarly act via the CCRK/MAK kinase pathway to regulate ciliary homeostasis in humans.

scholarly journals TAPping into the treasures of tubulin using novel protein production methods

2018 ◽  
Vol 62 (6) ◽  
pp. 781-792
Author(s):  
Nuo Yu ◽  
Niels Galjart
Keyword(s):  
Mammalian Cells ◽  
Gene Families ◽  
Cell Types ◽  
Cellular Functions ◽  
Tubulin Isotypes ◽  
Associated Proteins ◽  
Cytoskeletal Elements ◽  
Different Cell Types ◽  
Β Tubulin

Microtubules are cytoskeletal elements with important cellular functions, whose dynamic behaviour and properties are in part regulated by microtubule-associated proteins (MAPs). The building block of microtubules is tubulin, a heterodimer of α- and β-tubulin subunits. Longitudinal interactions between tubulin dimers facilitate a head-to-tail arrangement of dimers into protofilaments, while lateral interactions allow the formation of a hollow microtubule tube that mostly contains 13 protofilaments. Highly homologous α- and β-tubulin isotypes exist, which are encoded by multi-gene families. In vitro studies on microtubules and MAPs have largely relied on brain-derived tubulin preparations. However, these consist of an unknown mix of tubulin isotypes with undefined post-translational modifications. This has blocked studies on the functions of tubulin isotypes and the effects of tubulin mutations found in human neurological disorders. Fortunately, various methodologies to produce recombinant mammalian tubulins have become available in the last years, allowing researchers to overcome this barrier. In addition, affinity-based purification of tagged tubulins and identification of tubulin-associated proteins (TAPs) by mass spectrometry has revealed the ‘tubulome’ of mammalian cells. Future experiments with recombinant tubulins should allow a detailed description of how tubulin isotype influences basic microtubule behaviour, and how MAPs and TAPs impinge on tubulin isotypes and microtubule-based processes in different cell types.

scholarly journals Calcineurin Regulates Cyclin D1 Accumulation in Growth-stimulated Fibroblasts

2004 ◽  
Vol 15 (4) ◽  
pp. 1833-1842 ◽  
Author(s):  
Christina R. Kahl ◽  
Anthony R. Means
Keyword(s):  
Cyclosporin A ◽  
Cyclin D1 ◽  
Mammalian Cells ◽  
Human Fibroblasts ◽  
Ectopic Expression ◽  
D1 Protein ◽  
Cell Types ◽  
Cycle Arrest ◽  
Cyclin D1 Protein ◽  
Multiple Cell

Calcium (Ca2+) and calmodulin (CaM) are required for progression of mammalian cells from quiescence into S phase. In multiple cell types, cyclosporin A causes a G1 cell cycle arrest, implicating the serine/threonine phosphatase calcineurin as one Ca2+/CaM-dependent enzyme required for G1 transit. Here, we show, in diploid human fibroblasts, that cyclosporin A arrested cells in G1 before cyclin D/cdk4 complex activation and retinoblastoma hyperphosphorylation. This arrest occurred in early G1 with low levels of cyclin D1 protein. Because cyclin D1 mRNA was induced normally in the cyclosporin A-treated cells, we analyzed the half-life of cyclin D1 in the presence of cyclosporin A and found no difference from control cells. However, cyclosporin A treatment dramatically reduced cyclin D1 protein synthesis. Although these pharmacological experiments suggested that calcineurin regulates cyclin D1 synthesis, we evaluated the effects of overexpression of activated calcineurin on cyclin D1 synthesis. In contrast to the reduction of cyclin D1 with cyclosporin A, ectopic expression of calcium/calmodulin-independent calcineurin promoted synthesis of cyclin D1 during G1 progression. Therefore, calcineurin is a Ca2+/CaM-dependent target that regulates cyclin D1 accumulation in G1.

scholarly journals A Synthetic Transcription Platform for Programmable Gene Expression in Mammalian Cells

2020 ◽  
Author(s):  
William C.W. Chen ◽  
Leonid Gaidukov ◽  
Ming-Ru Wu ◽  
Jicong Cao ◽  
Gigi C.G. Choi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interferon Gamma ◽  
Mammalian Cells ◽  
Cell Types ◽  
Regulatory Elements ◽  
Genetic Circuits ◽  
Control Of Gene Expression ◽  
Transcription System ◽  
Multiple Cell ◽  
Cellular Phenotypes

Precise, scalable, and sustainable control of genetic and cellular activities in mammalian cells is key to developing precision therapeutics and smart biomanufacturing. We created a highly tunable, modular, versatile CRISPR-based synthetic transcription system for the programmable control of gene expression and cellular phenotypes in mammalian cells. Genetic circuits consisting of well-characterized libraries of guide RNAs, binding motifs of synthetic operators, transcriptional activators, and additional genetic regulatory elements expressed mammalian genes in a highly predictable and tunable manner. We demonstrated the programmable control of reporter genes episomally and chromosomally, with up to 25-fold more EF1[alpha]; promoter activity, in multiple cell types. We used these circuits to program secretion of human monoclonal antibodies and to control T cell effector function marked by interferon-[gamma] production. Antibody titers and interferon-[gamma]; concentrations were significantly correlated with synthetic promoter strengths, providing a platform for programming gene expression and cellular function for biological, biomanufacturing, and biomedical applications.

scholarly journals Surface apposition and multiple cell contacts promote myoblast fusion in Drosophila flight muscles

2015 ◽  
Vol 211 (1) ◽  
pp. 191-203 ◽  
Author(s):  
Nagaraju Dhanyasi ◽  
Dagan Segal ◽  
Eyal Shimoni ◽  
Vera Shinder ◽  
Ben-Zion Shilo ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Actin Polymerization ◽  
Cell Types ◽  
Myoblast Fusion ◽  
Cell Contact ◽  
Minimal Distance ◽  
Multiple Cell ◽  
Flight Muscles ◽  
Cytoskeletal Elements ◽  
Cell Cell

Fusion of individual myoblasts to form multinucleated myofibers constitutes a widely conserved program for growth of the somatic musculature. We have used electron microscopy methods to study this key form of cell–cell fusion during development of the indirect flight muscles (IFMs) of Drosophila melanogaster. We find that IFM myoblast–myotube fusion proceeds in a stepwise fashion and is governed by apparent cross talk between transmembrane and cytoskeletal elements. Our analysis suggests that cell adhesion is necessary for bringing myoblasts to within a minimal distance from the myotubes. The branched actin polymerization machinery acts subsequently to promote tight apposition between the surfaces of the two cell types and formation of multiple sites of cell–cell contact, giving rise to nascent fusion pores whose expansion establishes full cytoplasmic continuity. Given the conserved features of IFM myogenesis, this sequence of cell interactions and membrane events and the mechanistic significance of cell adhesion elements and the actin-based cytoskeleton are likely to represent general principles of the myoblast fusion process.

scholarly journals The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5187
Author(s):  
Yiming Yang ◽  
Andrew J. Sanders ◽  
Q. Ping Dou ◽  
David G. Jiang ◽  
Amber Xinyu Li ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Cell Types ◽  
Potential Therapeutic Target ◽  
Adhesion Protein ◽  
Pathological Conditions ◽  
A Cell ◽  
Multiple Cell ◽  
Primary Focus

Activated leukocyte cell adhesion molecule (ALCAM), also known as CD166, is a cell adhesion protein that is found in multiple cell types. ALCAM has multiple and diverse roles in various physiological and pathological conditions, including inflammation and cancer. There has been compelling evidence of ALCAM’s prognostic value in solid cancers, indicating that it is a potential therapeutic target. The present article overviews the recent findings and progress in ALCAM and its involvement in cancer, with a primary focus on its clinical connections in cancer and therapeutic values.

scholarly journals Spatiotemporal Regulation of Cell–Cell Adhesions

2021 ◽  
Author(s):  
Brent M. Bijonowski
Keyword(s):  
Cell Adhesion ◽  
Red Light ◽  
Cell Types ◽  
Spatiotemporal Regulation ◽  
Different Types ◽  
Multiple Cell ◽  
Cell Adhesions ◽  
Different Cell Types ◽  
Insight Into ◽  
Cell Cell

Cell–cell adhesions are fundamental in regulating multicellular behavior and lie at the center of many biological processes from embryoid development to cancer development. Therefore, controlling cell–cell adhesions is fundamental to gaining insight into these phenomena and gaining tools that would help in the bioartificial construction of tissues. For addressing biological questions as well as bottom-up tissue engineering the challenge is to have multiple cell types self-assemble in parallel and organize in a desired pattern from a mixture of different cell types. Ideally, different cell types should be triggered to self-assemble with different stimuli without interfering with the other and different types of cells should sort out in a multicellular mixture into separate clusters. In this chapter, we will summarize the developments in photoregulation cell–cell adhesions using non-neuronal optogenetics. Among the concepts, we will cover is the control of homophylic and heterophilic cell–cell adhesions, the independent control of two different types with blue or red light and the self-sorting of cells into distinct structures and the importance of cell–cell adhesion dynamics. These tools will give an overview of how the spatiotemporal regulation of cell–cell adhesion gives insight into their role and how tissues can be assembled from cells as the basic building block.

The abts and sulp families of anion transporters from Caenorhabditis elegans

2005 ◽  
Vol 289 (2) ◽  
pp. C341-C351 ◽  
Author(s):  
Teresa Sherman ◽  
Marina N. Chernova ◽  
Jeffrey S. Clark ◽  
Lianwei Jiang ◽  
Seth L. Alper ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Mammalian Cells ◽  
Expression Patterns ◽  
Basolateral Membrane ◽  
Gene Families ◽  
Cell Types ◽  
Anion Transport ◽  
Gene Products ◽  
Bicarbonate Transporter ◽  
Conserved Gene

The slc4 and slc26 gene families encode two distinct groups of gene products that transport HCO3− and other anions in mammalian cells. The SLC4 and SLC26 proteins are important contributors to transepithelial movement of fluids and electrolytes and to cellular pH and volume regulation. Herein we describe the cDNA cloning from the nematode Caenorhabditis elegans of four anion bicarbonate transporter ( abts) homologs of slc4 cDNA and eight sulfate permease ( sulp) homologs of slc26 cDNA. Analysis of transgenic nematode strains carrying promoter::GFP fusions suggests relatively restricted expression patterns for many of these genes. At least three genes are expressed primarily in the intestine, three are expressed primarily in the excretory cell, and one is expressed in both of these polarized cell types. One of the genes is also expressed exclusively in the myoepithelium-like cells of the pharynx. Many of the sulp gene products localize to the basolateral membrane rather than to the apical membrane. Several ABTS and SULP proteins exhibited anion transport function in Xenopus oocytes. The strongest Cl− transporter among these also mediated Cl−/HCO3− exchange. These findings encourage exploitation of the genetic strengths of the nematode model system in the study of the physiological roles of anion transport by the proteins of these two highly conserved gene families.

Sign in / Sign up

Export Citation Format

Share Document