DOCSLIB.ORG

Cell Communication and Signaling Mechanisms Terms to Learn

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cell Communication and Signaling Mechanisms Terms to Learn LQB383 Testbank Week 8 – Cell Communication and Signaling Mechanisms Terms to learn – match the terms to the definitions -------------------------------------------------------------------------------------------------------------------------- Adaptor Intracellular signaling protein Morphogen Endocrine cell Gap junction Neurotransmitter Hormone Receptor Extracellular signal molecule Signaling cascade Steroid hormone Synaptic signaling Paracrine signaling Second messenger Autocrine signaling Nuclear receptor family Interaction domain Contact-dependent signaling Definitions 1. General term for a protein that binds a specific extracellular molecule (ligand) and initiates a response in a cell. 2. Communicating cell-cell junction that allows ions and small molecules to pass from the cytoplasm of one cell to the cytoplasm of another. 3. Hydrophobic signaling molecule with characteristic four-ringed structure derived from cholesterol. 4. Short-range cell-cell communication via secreted local mediators that act on adjacent cells. 5. Specialised cell that secretes a hormone into the blood 6. The cell responds to its own secreted molecules. 7. Small signaling molecule secreted by the presynaptic nerve cell at a chemical synapse to relay the signal to the postsynaptic cell. 8. Small molecule that is formed in the cytosol, or released into it, in response to an extracellular signal, and that helps to relay the signal in the interior of the cell. 9. Molecule from the outside of the cell that communicates the behaviour or actions of other cells in the environment and elicits an appropriate response. 10. General term for a signal relay chain containing multiple amplification steps. 1 Receptor 2 Gap junction 3 Steroid hormone 4 Paracrine signaling 5 Endocrine cell 6 Autocrine signaling 7 Neurotransmitter 8 Second messenger 9 Extracellular signal molecule 10 Signaling cascade Multiple Choice Questions 1. Which of the following types of chemical signals is secreted in the blood and travels long distances to its target. A) Neurotransmitters B) Cytokines C) Hormones D) Target Proteins E) Kinases 2. Which of the following is a characteristic of a receptor? A) Speed B) Specificity C) Saturation D) Competition E) All except A 3. A steroid hormone is different from other types of hormones in that: A) the steroid hormone is made of amino acids B) the steroid hormone causes a change to how the cell functions C) the steroid hormone binds to intracellular receptor in the target cell D) the steroid hormone usually does not enter target cells E) the steroid hormone directly activates DNA responsive elements 4. The sequence of events involved in cell signaling is A) transduction reception response B) response reception transduction C) reception response transduction D) reception transduction response E) response transduction reception 5. Steroid hormones are carried on specific carrier proteins because the hormones: A) are too unstable to survive in the blood on their own. B) cannot dissolve readily in the blood because they are too hydrophobic. C) cannot find their target cells without them. D) need them in order to pass through the plasma membrane. E) require subsequent binding to specific receptor proteins in the nucleus. 6. In paracrine signaling, the signaling molecule A) acts on cells in close proximity to the secreting cell B) acts on target cells far away from the secreting cell C) acts on the same cells that secreted the signaling molecule D) is carried to the target cells by the blood 7. Steriod hormone response elements (HREs) are __________ , which, when bound to _____________, alter gene expession at the level of ________________. A) intron sequences; activated hormone receptor; translation. B) nuclear proteins; hormone; transcription. C) plasma membrane proteins; hormone; transcription. D) sequences in DNA; receptor-hormone complex; replication. E) sequences in DNA; receptor-hormone complex; transcription. 8. Which of the following is not involved in the specificity of signal transduction? A) Interactions between receptor and signal molecules B) Location of receptor molecules C) Structure of receptor molecules D) Structure of signal molecules E) Transmembrane transport of signal molecules by receptor molecules 9. The binding of a signaling molecule to its receptor is mediated by A) covalent bonds B) hydrophobic interactions C) ionic interactions D) B and C E) all of the above 10. Lipid–soluble signal molecules, such as testosterone, cross the membranes of all cells but affect only target cells because A) only target cells retain the appropriate DNA segments. B) intracellular receptors are present only in target cells. C) most cells lack the Y chromosome required. D) only target cells possess the cytosolic enzymes that transduce the testosterone. E) only in target cells is testosterone able to initiate the phosphorylation cascade leading to activated transcription factor. 11. Most signal molecules A) easily diffuse through the membrane and bind to receptors in the cytoplasm or nucleus. B) bind to membrane receptors and transmit information across a membrane without traversing the membrane. C) carry out functions in the nucleus after binding to a receptor in the cell membrane. D) A and C. E) A, B, and C. 12. A signal molecule is also known as a(n) _____. A) ligand B) protein C) initiator D) key E) receptor Refer to the Figures below and answer the following question by choosing the appropriate letter A, B, C, D or E. Figure 1 Figure 2 13. In Figure 1, which of these is a signal molecule? A 14. In Figure 1, which of these is a receptor molecule? B 15. In Figure 2, which of these receptors is NOT a membrane receptor? E Short Answer and Thought Questions 1. Describe the differences between endocrine, paracrine, and autocrine signaling. Ans: In endocrine signaling, signaling molecules are synthesized by one organ and act on distant target cells. In animals the signaling molecule is carried to target cells by the blood or other extracellular fluids. In paracrine signaling, the signaling molecules are released and affect only target cells in close proximity. In autocrine signaling, the cell that releases the signaling molecule is also affected by the released signaling molecule. 2. What are some of the common structural features of the receptors to which signal molecules bind? Ans: The molecule must have a signal-binding site on the extracellular side of the membrane, and must have an intracellular domain. Binding of the ligand to the receptor must induce change into another form (transduced) that affects the shape of the intracellular portion, so the signal can be transmitted. 3. What is a disadvantage of using common molecules for signaling paths? Ans: When second messengers are involved in more than one signaling pathway, fine tuning and sensitive responses can result. However, when the cross-talk becomes inappropriate, the signaling paths and responses will be in error. 4. What happens when signaling paths are not terminated properly? Ans: The cell will not be able to respond properly to new stimuli. The errant signals may lead to cancer, uncontrolled cell growth, or other problems. 5. Compare and contrast signaling by neurons to signaling by endocrine cells. What are the relative advantages of these two mechanisms for cellular communication? Ans: Both types of signaling can occur over long distances: neurons can send action potentials along very long axons (from the spinal cord to the fingers, for example), and hormones are passed through the bloodstream throughout the organism. Neurons secrete large amounts of neurotransmitters into a small, well-defined space at the synapse, yielding a high local concentration. Neurotransmitter receptors, therefore, need to bind to neurotransmitters with only low affinity (high Kd). By contrast, hormones are diluted extensively in the bloodstream, where they circulate at minuscule concentrations; hormone receptors, therefore, generally bind their hormones with extremely high affinity (low Kd). Neuronal signaling is very fast, limited only by the speed of propagation of the action potential and the workings of the synapse. In addition to speed, nerves communicate directly with one or a few cells. Hormonal signaling is slower, limited by blood flow and diffusion over relatively large distances, but it communicates at the same time with all the diverse and widely dispersed target cells in the body. 6. Cell communicate in ways that resemble human communication. Decide which of the following forms of human communication are analogous to autocrine, paracrine, endocrine and synaptic signaling by cells. A. A telephone conversation B. Talking to people at a cocktail party C. A radio announcement D. Talking to yourself Ans: A. A telephone conversation is analogous to synaptic signaling in the sense that it is a private communication from one person to another, usually some distance away and sometimes very far away. It differs from synaptic signaling because it is (usually) a two-way exchange, whereas synaptic signaling is a one-way communication. B. Talking to people at a cocktail party is analogous to paracrine signaling, which occurs between different cells (individuals) and is locally confined. C. A radio announcement is analogous to an endocrine signal, which is sent out to the whole body (the audience) with only target cells (individuals tuned to the specific radio station) affected by it. D. Talking to yourself is analogous to an autocrine signal, which is a signal that is sent and received by the
Load more

Recommended publications
  • Raman Imaging of Small Biomolecules
    BB48CH15_Min ARjats.cls April 16, 2019 13:8 Annual Review of Biophysics Raman Imaging of Small Biomolecules Yihui Shen, Fanghao Hu, and Wei Min Department of Chemistry, Columbia University, New York, NY 10027, USA; email: [email protected] Annu. Rev. Biophys. 2019. 48:347–69 Keywords First published as a Review in Advance on Raman microscopy, small molecule imaging, vibrational tags, lipid March 20, 2019 metabolism, drug imaging The Annual Review of Biophysics is online at biophys.annualreviews.org Abstract Access provided by Columbia University on 06/21/19. For personal use only. https://doi.org/10.1146/annurev-biophys-052118- Imaging techniques greatly facilitate the comprehensive knowledge of Annu. Rev. Biophys. 2019.48:347-369. Downloaded from www.annualreviews.org 115500 biological systems. Although imaging methodology for biomacromolecules Copyright © 2019 by Annual Reviews. such as protein and nucleic acids has been long established, micro- All rights reserved scopic techniques and contrast mechanisms are relatively limited for small biomolecules, which are equally important participants in biological pro- cesses. Recent developments in Raman imaging, including both microscopy and tailored vibrational tags, have created exciting opportunities for non- invasive imaging of small biomolecules in living cells, tissues, and organ- isms. Here, we summarize the principle and workflow of small-biomolecule imaging by Raman microscopy. Then, we review recent efforts in imaging, for example, lipids, metabolites, and drugs. The unique advantage of Raman imaging has been manifested in a variety of applications that have provided novel biological insights. 347 BB48CH15_Min ARjats.cls April 16, 2019 13:8 Contents THENEEDFORIMAGINGSMALLBIOMOLECULES........................ 348 IMAGINGSMALLMOLECULESBYVIBRATIONALCONTRAST............. 349 LINEAR AND NONLINEAR RAMAN SCATTERING SPECTROSCOPY ANDMICROSCOPY.........................................................
    [Show full text]
  • Small Molecules, Big Impact
    FOR RESEARCH USE ONLY. NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES. STEMCELL TECHNOLOGIES INC.’S QUALITY MANAGEMENT SYSTEM IS CERTIFIED TO ISO 13485 MEDICAL DEVICE STANDARDS. TGFβ: The TGFβ superfamily members are major regulators of self-renewal and differentiation to mesendodermal lineages. p38 / p53: p38 MAPK is activated in response to cellular stresses, and influences apoptosis and cellular differentiation. p53 is activated in Pathway Activators: IDE1, IDE2; Pathway Inhibitors: SB431542, LY364947, RepSox, Dorsomorphin, LDN193189 response to cellular stresses and regulates growth arrest, apoptosis and/or DNA repair. Inhibition of p53 is used to facilitate reprogramming. Pathway Inhibitors: BIRB-796, SB202190, SB203580, Cyclic Pifithrin-α, Pifithrin-μ Hedgehog: The Hedgehog pathway is important in the differentiation of mesenchymal subtypes (e.g. osteocytes) and in neural subtypes (e.g. dopaminergic neurons). FGF: FGF signaling via MEK/ERK is critical for self-renewal and proliferation of human PSCs. However, other receptor tyrosine kinases can Pathway Activator: Purmorphamine; Pathway Inhibitors: Cyclopamine, HPI-1 also act through the MEK/ERK and PI3K signaling pathways. Pathway Activators: Pyrintegrin, PS-48; Pathway Inhbitors: Pluripotin, PD0325901, PD98059, Reversine IWP-2 WNT: The WNT pathway regulates differentiation to the mesoendodermal lineages, induces self-renewal of PSCs, and aids in reprogramming. IWP-3 Pathway Activators: BIO, CHIR99021, Kenpaullone, SB216763; Pathway Inhibitors: IWP-2, IWP-3, IWP-4,
    [Show full text]
  • Monoclonal Antibodies and Small-Molecule Drugs: WHAT GENERAL NEUROLOGISTS NEED to KNOW
    THIS CONTENT IS SPONSORED BY AMGEN INC. AND NOVARTIS PHARMACEUTICALS CORPORATION USA-334-83498 Monoclonal Antibodies and Small-Molecule Drugs: WHAT GENERAL NEUROLOGISTS NEED TO KNOW APRIL 2020 I VOL. 28 NO. 4 A Member of the Network Introduction plasma concentration 1–8 days) than IV, but this route permits self- Numerous drug modalities have been approved to treat neurologic administration at home.9,22 diseases, including small-molecule drugs (SMDs) and biologics SMDs generally have wide distribution into tissues, organs and such as monoclonal antibodies (mAbs).1-3 While both are consid- plasma.10,23 They are metabolized by CYP450 enzymes via oxidation, ered targeted therapies,2-7 each has unique characteristics that may leading to renal elimination in the urine, and by conjugation reac- affect their use in clinical practice.5,8,9 This article describes the gen- tions (eg, glucuronidation), leading to hepatic/biliary elimination in eral characteristics of SMDs and mAbs and discusses some of their the stool.10,24,25 mAbs have a small range of distribution.10,23 Particu- safety implications relevant to their use by general neurologists in larly relevant to neurology, therapeutic mAbs do not readily cross clinical practice. the blood–brain barrier and therefore have minimal distribution in the central nervous system (CNS).8,9 Therapeutic mAbs are also Characteristics of SMDs and mAbs too large for clearance by renal or hepatic mechanisms, and instead The general characteristics and pharmacokinetics (PK) of are metabolized by two primary
    [Show full text]
  • Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery
    International Journal of Molecular Sciences Review Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery Qingxin Li 1,* and CongBao Kang 2,* 1 Guangdong Provincial Engineering Laboratory of Biomass High Value Utilization, Guangdong Provincial Bioengineering Institute (Guangzhou Sugarcane Industry Research Institute), Guangdong Academy of Sciences, Guangzhou 510316, China 2 Experimental Drug Development Centre (EDDC), Agency for Science, Technology and Research (A*STAR), 10 Biopolis Road, Chromos, #05-01, Singapore 138670, Singapore * Correspondence: [email protected] (Q.L.); [email protected] (C.K.); Tel.: +86-020-84168436 (Q.L.); +65-64070602 (C.K.) Received: 12 June 2020; Accepted: 20 July 2020; Published: 24 July 2020 Abstract: Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins. These compounds have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. A target-based drug discovery project usually includes target identification, target validation, hit identification, hit to lead and lead optimization. Understanding molecular interactions between small molecules and their targets is critical in drug discovery. Although many biophysical and biochemical methods are able to elucidate molecular interactions of small molecules with their targets, structural biology is the most powerful tool to determine the mechanisms of action for both targets and the developed compounds. Herein, we reviewed the application of structural biology to investigate binding modes of orthosteric and allosteric inhibitors. It is exemplified that structural biology provides a clear view of the binding modes of protease inhibitors and phosphatase inhibitors.
    [Show full text]
  • Met Receptor Tyrosine Kinase: Enhanced Signaling Through Adapter Proteins
    Oncogene (2000) 19, 5582 ± 5589 ã 2000 Macmillan Publishers Ltd All rights reserved 0950 ± 9232/00 $15.00 www.nature.com/onc Met receptor tyrosine kinase: enhanced signaling through adapter proteins Kyle A Furge1, Yu-Wen Zhang1 and George F Vande Woude*,1 1Van Andel Research Institute, 333 Bostwick, N.E., Grand Rapids, Michigan, MI 49503, USA The Met receptor tyrosine kinase is the prototypic matrix (`invasion') (Jeers et al., 1996c; Matsumoto et member of a small subfamily of growth factor receptors al., 1994; Rong et al., 1994; Weidner et al., 1990). In that when activated induce mitogenic, motogenic, and addition, HGF/SF-Met signaling can induce several morphogenic cellular responses. The ligand for Met is dierent epithelial and mesenchymal cell types to hepatocyte growth factor/scatter factor (HGF/SF) and undergo an involved dierentiation program termed while normal HGF/SF-Met signaling is required for branching morphogenesis when the cells are grown in a embryonic development, abnormal Met signaling has three dimensional matrix (Brinkmann et al., 1995; been strongly implicated in tumorigenesis, particularly in Jeers et al., 1996c; Montesano et al., 1991a; Niemann the development of invasive and metastatic phenotypes. et al., 1998). During branching morphogenesis, groups Following ligand binding and autophosphorylation, Met of cells proliferate, migrate, and dierentiate to form a transmits intercellular signals using a unique multi- connected series of tubules arranged like branches from substrate docking site present within the C-terminal a tree. However, even in the absense of a three end of the receptor. The multisubstrate docking site dimensional matrix, signaling through the Met receptor mediates the binding of several adapter proteins such as can induce morphogenesis and lumen formation in Grb2, SHC, Crk/CRKL, and the large adapter protein certain cell types (Jeers et al., 1996a; Tsarfaty et al., Gab1.
    [Show full text]
  • Paracrine Wnt1 Drives Interstitial Fibrosis Without Inflammation by Tubulointerstitial Cross-Talk
    BASIC RESEARCH www.jasn.org Paracrine Wnt1 Drives Interstitial Fibrosis without Inflammation by Tubulointerstitial Cross-Talk † Omar H. Maarouf,* Anusha Aravamudhan,* Deepika Rangarajan,* Tetsuro Kusaba,* ‡ Victor Zhang,* Jeremy Welborn,* Daniel Gauvin,* Xiuyun Hou,* Rafael Kramann,* and † Benjamin D. Humphreys* § *Renal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; †Harvard Medical School, Boston, Massachusetts; ‡Division of Nephrology and Clinical Immunology and Medical Faculty, Rheinisch- Westfälische Technische Hochschule Aachen University, Aachen, Germany; and §Harvard Stem Cell Institute, Cambridge, Massachusetts ABSTRACT AKI with incomplete epithelial repair is a major contributor to CKD characterized by tubulointerstitial fibrosis. Injury–induced epithelial secretion of profibrotic factors is hypothesized to underlie this link, but the identity of these factors and whether epithelial injury is required remain undefined. We previously showed that activation of the canonical Wnt signaling pathway in interstitial pericytes cell autonomously drives myofibroblast acti- vation in vivo. Here, we show that inhibition of canonical Wnt signaling also substantially prevented TGFb– dependent myofibroblast activation in vitro. To investigate whether Wnt ligand derived from proximal tubule is sufficient for renal fibrogenesis, we generated a novel mouse strain with inducible proximal tubule Wnt1 secretion. Adult mice were treated with vehicle or tamoxifen and euthanized at 12 or 24 weeks postinjection. Compared
    [Show full text]
  • Small Molecule and Protein Docking Introduction
    Small Molecule and Protein Docking Introduction • A significant portion of biology is built on the paradigm sequence structure function • As we sequence more genomes and get more structural information, the next challenge will be to predict interactions and binding for two or more biomolecules (nucleic acids, proteins, peptides, drugs or other small molecules) Introduction • The questions we are interested in are: – Do two biomolecules bind each other? – If so, how do they bind? – What is the binding free energy or affinity? • The goals we have are: – Searching for lead compounds – Estimating effect of modifications – General understanding of binding – … Rationale • The ability to predict the binding site and binding affinity of a drug or compound is immensely valuable in the area or pharmaceutical design • Most (if not all) drug companies use computational methods as one of the first methods of screening or development • Computer-aided drug design is a more daunting task, but there are several examples of drugs developed with a significant contribution from computational methods Examples • Tacrine – inhibits acetylcholinesterase and boost acetylcholine levels (for treating Alzheimer’s disease) • Relenza – targets influenza • Invirase, Norvir, Crixivan – Various HIV protease inhibitors • Celebrex – inhibits Cox-2 enzyme which causes inflammation (not our fault) Docking • Docking refers to a computational scheme that tries to find the best binding orientation between two biomolecules where the starting point is the atomic coordinates of the two molecules • Additional data may be provided (biochemical, mutational, conservation, etc.) and this can significantly improve the performance, however this extra information is not required Bound vs. Unbound Docking • The simplest problem is the “bound” docking problem.
    [Show full text]
  • Reporting Data from High-Throughput Screening of Small-Molecule Libraries
    COMMENTARY Reporting data from high-throughput screening of small-molecule libraries James Inglese, Caroline E Shamu & R Kiplin Guy Publications reporting results of small-molecule screens are becoming more common as academic researchers increasingly make use of high-throughput screening (HTS) facilities. However, no standards have been formally established for reporting small-molecule screening data, and often key information important for the evaluation and interpretation of results is omitted in published HTS protocols. Here, we propose concise guidelines for reporting small-molecule HTS data. High-throughput screening (HTS) is becoming providing a basis for evaluation, comparison in the assay. Controls are used to determine a routine method for identifying probes used in and replication of small-molecule screens. We an assay ‘window’ and validate the biological chemical biology. The flexibility of the process have divided small-molecule screen protocol response. It is often desirable to provide an has allowed numerous and disparate areas of information into five categories: the assay, the indication as to the efficacy of the controls. biology to engage with an equally diverse palate library, the HTS process, the post-HTS analy- For example, here is an assay strategy descrip- of chemistry. However, with this diversity, the sis of data and compound structures, and the tion that might be written for a fluorescence many components associated with HTS—the screen results (Fig. 1). Within each category, polarization assay: bioassay, the assay format, the nature of the we describe key pieces of information that are library, reagent and sample delivery meth- important for interpretation and replication This screen was carried out to identify compounds ods, the detection instrumentation, the level of a screen (Table 1).
    [Show full text]
  • Small Molecule Drug Discovery
    Small Molecule Drug Discovery Centre for TIA Pipeline Drug Candidate Accelerator Optimisation TetraQ Other NCRIS facilities Universities, Medical research institutes Other therapeutic areas within TIA Small Molecule Discovery and Development Biological Target Compounds Australian Centre for Integrated Australia Translational Preclinical Drug Medicinal Development Chemistry Facility Australia is ideally positioned to be a major player in the global Pharma ecosystem where risk‑adverse companies are looking to in‑license assets that have demonstrated development potential. To enhance the progression of early stage discoveries through to preclinical development, TIA has formed a Small Molecules Group, an integrated capability network of National Research Infrastructure across Australia. These facilities are committed to providing high quality research infrastructure to support leading‑edge research and to boost innovation in Australia. SUPPORTED BY: CONTACT US: T: (07) 3735 4433 E: [email protected] Level 14, 330 Collins Street, Melbourne VIC 3000 www.therapeuticinnovation.com.au Compounds Australia Capability/services offered: • National compound management and logistics facility for small molecule compound libraries and natural product extract and fraction libraries. • Cost effective compound management, supporting drug discovery through high throughput screening • Provides storage and management of the national open access compound collection, GRIDD’s NatureBank collection and numerous proprietary compound collections.
    [Show full text]
  • Identification and Characterization of a Small Molecule Inhibitor of Formin
    Chemistry & Biology Article Identification and Characterization of a Small Molecule Inhibitor of Formin-Mediated Actin Assembly Syed A. Rizvi,1,5 Erin M. Neidt,2,5 Jiayue Cui,1 Zach Feiger,3 Colleen T. Skau,2 Margaret L. Gardel,3 Sergey A. Kozmin,1 and David R. Kovar2,4,* 1Department of Chemistry 2Department of Molecular Genetics and Cell Biology 3Department of Physics 4Department of Biochemistry and Molecular Biology The University of Chicago, Chicago, IL 60637, USA 5These authors contributed equally to this work *Correspondence: [email protected] DOI 10.1016/j.chembiol.2009.10.006 SUMMARY nant tumor function and are highly overexpressed in different cancer cell types including colorectal, carcinoma, leukemia, Formins stimulate actin filament assembly for funda- melanoma, and lymphoid (Favaro et al., 2003; Kitzing et al., mental cellular processes including division, adhe- 2007; Sarmiento et al., 2008; Zhu et al., 2008). Determining for- sion, establishing polarity, and motility. A formin min’s numerous roles is particularly complicated because most inhibitor would be useful because most cells express organisms express multiple isoforms (Goode and Eck, 2007). multiple formins whose functions are not known and For example, there are at least 20 formin genes in plants, 18 in because metastatic tumor formation depends on the mammals, 6 each in Drosophila melanogaster and Caenorhabdi- tis elegans, 3 in fission yeast, and 2 in budding yeast (Higgs, deregulation of formin-dependent processes. We 2005). A major challenge is to elucidate all formin-dependent identified a general small molecule inhibitor of formin cellular functions in both healthy and diseased tissues. homology 2 domains (SMIFH2) by screening com- Formins are multidomain proteins that contain a highly pounds for the ability to prevent formin-mediated conserved actin assembly formin homology 2 FH2 domain and actin assembly in vitro.
    [Show full text]
  • Paracrine Signaling Mediated at Cellcell Contacts
    Insights & Perspectives Think again Paracrine signaling mediated at cellÀcell contacts Sougata Roy*,† and Thomas B. Kornberg Recent findings in several organ systems show that cytoneme-mediated systems. However, recent work that we signaling transports signaling proteins along cellular extensions and targets discuss here describes paracrine signal- cell-to-cell exchanges to synaptic contacts. This mechanism of paracrine ing that is instead contact-mediated and signaling may be a general one that is used by many (or all) cell types in many (or dependent on transient synapses that all) organs. We briefly review these findings in this perspective. We also non-neuronal cells make. These synap- describe the properties of several signaling systems that have previously been ses form at sites where specialized signaling filopodia called cytonemes interpreted to support a passive diffusion mechanism of signaling protein extend to contact target cells. dispersion, but can now be understood in the context of the cytoneme mechanism. Keywords: The classical model of .cytonemes; filopodia; morphogen; paracrine signaling; synapse; TGF-b paracrine signaling assumes that signals disperse by passive Introduction so that signals are within only 15À20 nm diffusion of their target receptors when they are Animal cells communicate over long released. Paracrine signaling, the third There are many paracrine signaling distances in various ways. Endocrine general mechanism, may be considered proteins that have been characterized. cells signal systemically by releasing to be a variant of endocrine signaling, They include the Fibroblast Growth hormones that disseminate in the vas- functioning at relatively short range Factors (FGFs) and other proteins that culature. Neurons also release signals, when secreted signals move limited activate Receptor Tyrosine Kinases, but they exchange information at syn- distances by passive diffusion in extra- TGF-b family members, Wnt proteins, apses that form where their axons and cellular fluid.
    [Show full text]
  • Paracrine Signaling by Progesterone ⇑ Renuga Devi Rajaram, Cathrin Brisken
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Infoscience - École polytechnique fédérale de Lausanne Molecular and Cellular Endocrinology xxx (2011) xxx–xxx Contents lists available at SciVerse ScienceDirect Molecular and Cellular Endocrinology journal homepage: www.elsevier.com/locate/mce Review Paracrine signaling by progesterone ⇑ Renuga Devi Rajaram, Cathrin Brisken Ecole Polytechnique Fédérale de Lausanne (EPFL), ISREC – Swiss Institute for Experimental Cancer Research, NCCR Molecular Oncology, SV2832 Station 19, CH-1015 Lausanne, Switzerland article info abstract Article history: Steroid hormones coordinate and control the development and function of many organs and are impli- Available online xxxx cated in many pathological processes. Progesterone signaling, in particular, is essential for several impor- tant female reproductive functions. Physiological effects of progesterone are mediated by its cognate Keywords: receptor, expressed in a subset of cells in target tissues. Experimental evidence has accumulated that pro- Progesterone receptor gesterone acts through both cell intrinsic as well as paracrine signaling mechanisms. By relegating the Paracrine signaling hormonal stimulus to paracrine signaling cascades the systemic signal gets amplified locally and signal- Uterus ing reaches different cell types that are devoid of hormone receptors. Interestingly, distinct biological Ovaries responses to progesterone in different target tissues rely on several tissue-specific and some common Mammary gland Carcinogenesis paracrine factors that coordinate biological responses in different cell types. Evidence is forthcoming that the intercellular signaling pathways that control development and physiological functions are important in tumorigenesis. Crown Copyright Ó 2011 Published by Elsevier Ireland Ltd. All rights reserved. Contents 1. Introduction . ....................................................................................................... 00 2.
    [Show full text]