DOCSLIB.ORG

Endocytosis of Nutrient Transporters in Fungi

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Endocytosis of Nutrient Transporters in Fungi Delft University of Technology Endocytosis of nutrient transporters in fungi The ART of connecting signaling and trafficking Barata-Antunes, Cláudia; Alves, Rosana; Talaia, Gabriel; Casal, Margarida; Gerós, Hernâni; Mans, Robert; Paiva, Sandra DOI 10.1016/j.csbj.2021.03.013 Publication date 2021 Document Version Final published version Published in Computational and Structural Biotechnology Journal Citation (APA) Barata-Antunes, C., Alves, R., Talaia, G., Casal, M., Gerós, H., Mans, R., & Paiva, S. (2021). Endocytosis of nutrient transporters in fungi: The ART of connecting signaling and trafficking. Computational and Structural Biotechnology Journal, 19, 1713-1737. https://doi.org/10.1016/j.csbj.2021.03.013 Important note To cite this publication, please use the final published version (if applicable). Please check the document version above. Copyright Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons. Takedown policy Please contact us and provide details if you believe this document breaches copyrights. We will remove access to the work immediately and investigate your claim. This work is downloaded from Delft University of Technology. For technical reasons the number of authors shown on this cover page is limited to a maximum of 10. Computational and Structural Biotechnology Journal 19 (2021) 1713–1737 journal homepage: www.elsevier.com/locate/csbj Review Endocytosis of nutrient transporters in fungi: The ART of connecting signaling and trafficking Cláudia Barata-Antunes a, Rosana Alves a, Gabriel Talaia a,b, Margarida Casal a, Hernâni Gerós a,c,d, ⇑ ⇑ Robert Mans e, , Sandra Paiva a, a Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Braga, Portugal b Department of Cell Biology, Yale University School of Medicine, New Haven, CT, United States c Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal d Centre of Biological Engineering (CEB), Department of Biological Engineering, University of Minho, Braga, Portugal e Department of Biotechnology, Delft University of Technology, Delft, the Netherlands article info abstract Article history: Plasma membrane transporters play pivotal roles in the import of nutrients, including sugars, amino Received 1 November 2020 acids, nucleobases, carboxylic acids, and metal ions, that surround fungal cells. The selective removal Received in revised form 14 March 2021 of these transporters by endocytosis is one of the most important regulatory mechanisms that ensures Accepted 14 March 2021 a rapid adaptation of cells to the changing environment (e.g., nutrient fluctuations or different stresses). Available online 19 March 2021 At the heart of this mechanism lies a network of proteins that includes the arrestin-related trafficking adaptors (ARTs) which link the ubiquitin ligase Rsp5 to nutrient transporters and endocytic factors. Keywords: Transporter conformational changes, as well as dynamic interactions between its cytosolic termini/loops Fungi and with lipids of the plasma membrane, are also critical during the endocytic process. Here, we review Nutrient transporters Endocytosis the current knowledge and recent findings on the molecular mechanisms involved in nutrient transporter Arrestins endocytosis, both in the budding yeast Saccharomyces cerevisiae and in some species of the filamentous Ubiquitylation fungus Aspergillus. We elaborate on the physiological importance of tightly regulated endocytosis for cel- Endocytic signals lular fitness under dynamic conditions found in nature and highlight how further understanding and Metabolism engineering of this process is essential to maximize titer, rate and yield (TRY)-values of engineered cell Signaling pathways factories in industrial biotechnological processes. Conformational changes Ó 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and MCCs/eisosomes Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons. Structure-function Biotechnology org/licenses/by/4.0/). Cell factories Saccharomyces cerevisiae Aspergilli Abbreviations: AAs, amino acids; ACT, amino Acid/Choline Transporter; AP, adaptor protein; APC, amino acid-polyamine-organocation; Arg, arginine; Arts, arrestin-related trafficking adaptors; Asp, aspartic acid; C, carbon; C-terminus, carboxyl-terminus; Cu, copper; DUBs, deubiquitinating enzymes; EMCs, eisosome membrane compartments; ER, endoplasmic reticulum; ESCRT, endosomal sorting complex required for transport; fAATs, fungal AA transporters; Fe, iron; GAAC, general amino acid control; Glu, glutamic acid; H+, proton; IF, inward-facing; LAT, L-type Amino acid Transporter; LID, loop Interaction Domain; Lys, lysine; MCCs, membrane compartments containing the arginine permease Can1; MCPs, membrane compartments of Pma1; Met, methionine; MFS, major facilitator superfamily; Mn, manganese; MVB, multi vesicular bodies; N, + nitrogen; NAT, nucleobase Ascorbate Transporter; NCS1, nucleobase/Cation Symporter 1; NCS2, nucleobase cation symporter family 2; NH4 , ammonium; N-terminus, amino- terminus; OF, outward-facing; PEST, proline (P), glutamic acid (E), serine (S), and threonine (T); PM, plasma membrane; PVE, prevacuolar endosome; TGN, trans-Golgi network; TMSs, transmembrane segments; TORC1, target of rapamycin complex 1; Trp, tryptophan; TRY, titer, rate and yield; Tyr, tyrosine; Ub, ubiquitin; VPS, vacuolar protein sorting; W/V, weight per volume; YAT, yeast Amino acid Transporter; Zn, Zinc. ⇑ Corresponding authors at: Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal (Sandra Paiva). Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ, Delft, The Netherlands (Robert Mans). E-mail addresses: [email protected] (R. Mans), [email protected] (S. Paiva). https://doi.org/10.1016/j.csbj.2021.03.013 2001-0370/Ó 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Cláudia Barata-Antunes, R. Alves, G. Talaia et al. Computational and Structural Biotechnology Journal 19 (2021) 1713–1737 Contents 1. Introduction . ..................................................................................................... 1714 2. Endocytosis of sugar transporters . .................................................................................. 1719 2.1. Endocytosis of sugar transporters triggered by excess of substrate. ..................................................... 1719 2.2. Endocytosis of sugar transporters triggered by substrate depletion or starvation . .................................. 1720 2.3. Endocytosis of sugar transporters triggered by different physiological inputs . .................................. 1720 3. Endocytosis of monocarboxylate transporters . ............................................................... 1721 4. Endocytosis of amino acid transporters .................................................................................. 1722 4.1. Endocytosis of amino acid transporters triggered by nitrogen availability or excess of substrate . ............... 1724 4.2. Endocytosis of amino acid transporters triggered by substrate depletion or acute starvation . ............... 1727 4.3. Endocytosis of amino acid transporters triggered by cell stress . ..................................................... 1727 5. Endocytosis of nucleobase transporters .................................................................................. 1727 5.1. Endocytosis of Fur-like transporters . ........................................................................ 1727 5.2. Endocytosis of the high-affinity purine transporters . ..................................................... 1728 6. Endocytosis of metal micronutrient transporters. ............................................................... 1729 6.1. Endocytosis of copper transporters . ........................................................................ 1729 6.2. Endocytosis of iron transporters. ........................................................................ 1729 6.3. Endocytosis of zinc transporters. ........................................................................ 1729 6.4. Endocytosis of a broad-specificity metal ion transporter . ..................................................... 1730 7. Biotechnological relevance of nutrient transporter endocytosis ............................................................... 1730 8. Conclusions and future perspectives. .................................................................................. 1731 CRediT authorship contribution statement . ............................................................... 1731 Declaration of Competing Interest . .................................................................................. 1731 Acknowledgements . .................................................................................. 1731 References . ..................................................................................................... 1731 1. Introduction (endosome-to-PM recycling
Load more

Recommended publications
  • The Significance of the Evolutionary Relationship of Prion Proteins and ZIP Transporters in Health and Disease
    The Significance of the Evolutionary Relationship of Prion Proteins and ZIP Transporters in Health and Disease by Sepehr Ehsani A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Laboratory Medicine and Pathobiology University of Toronto © Copyright by Sepehr Ehsani 2012 The Significance of the Evolutionary Relationship of Prion Proteins and ZIP Transporters in Health and Disease Sepehr Ehsani Doctor of Philosophy Department of Laboratory Medicine and Pathobiology University of Toronto 2012 Abstract The cellular prion protein (PrPC) is unique amongst mammalian proteins in that it not only has the capacity to aggregate (in the form of scrapie PrP; PrPSc) and cause neuronal degeneration, but can also act as an independent vector for the transmission of disease from one individual to another of the same or, in some instances, other species. Since the discovery of PrPC nearly thirty years ago, two salient questions have remained largely unanswered, namely, (i) what is the normal function of the cellular protein in the central nervous system, and (ii) what is/are the factor(s) involved in the misfolding of PrPC into PrPSc? To shed light on aspects of these questions, we undertook a discovery-based interactome investigation of PrPC in mouse neuroblastoma cells (Chapter 2), and among the candidate interactors, identified two members of the ZIP family of zinc transporters (ZIP6 and ZIP10) as possessing a PrP-like domain. Detailed analyses revealed that the LIV-1 subfamily of ZIP transporters (to which ZIPs 6 and 10 belong) are in fact the evolutionary ancestors of prions (Chapter 3).
    [Show full text]
  • Secreted Proteins in Microsporidian Parasites: a Functional and Evolutionary Perspective on Host-Parasite Interactions
    Secreted proteins in microsporidian parasites: a functional and evolutionary perspective on host-parasite interactions. Submitted by Scott Edward Campbell to the University of Exeter as a thesis for the degree of Doctor of Philosophy in Biological Science. In September 2013 This thesis is available for Library use on the understanding that it is copyright material and that no quotation from this thesis may be published without proper acknowledgment. I certify that all material in this thesis which is not my own work has been identified and that no material has previously been submitted and approved for the award of a degree by this or any other University. Signature ……………………………………. Page| 1 Abstract The Microsporidia form a phylum of obligate intracellular parasites known to cause disease in humans and a diverse range of economically important animal species. Once classified as ‘primitive’ eukaryotes, it is now recognised that the peculiarities of microsporidian genomics and cell biology are, in fact, the consequence of extreme reduction allowed by an intimate relationship with the host cell. Excluding survival as an extracellular spore, microsporidia are in direct contact with the host throughout their developmental lifecycle, from entry to egress. Host cell manipulations have been described in morphological terms, but despite this, characterisation of such processes at the molecular level remains challenging. The logistics of the microsporidian lifecycle suggest secreted proteins and membrane proteins with extracellular domains may be involved in virulence and implicated in host cell manipulation. This study employs bioinformatic tools to predict secreted proteins in diverse microsporidia and comparative genomics to identify conserved proteins which may be required for host cell manipulation, pathogenicity and lifecycle progression.
    [Show full text]
  • The Atiregs – Characterization of a New Family of Metal Transporters in Arabidopsis Thaliana
    Silvia Kirchner The AtIREGs – Characterization of a new family of metal transporters in Arabidopsis thaliana Institute of Plant Nutrition University of Hohenheim Prof. Dr. N. von Wirén The AtIREGs - Characterization of a new family of metal transporters in Arabidopsis thaliana Dissertation Submitted in fulfilment of the requirements for the degree „Doktor der Agrarwissenschaften“ (Dr. Sc. Agr. / Ph. D. in Agricultural Sciences) to the Faculty Agricultural Sciences of the University of Hohenheim presented by Silvia Kirchner from Neu-Ulm 2009 This thesis was accepted as a doctoral dissertation in fulfilment of the requirements for the degree “Doktor der Agrarwissenschaften” by the Faculty of Agricultural Sciences at the University of Hohenheim. Date of oral examination: 3rd March 2009 Examination Committee Supervisor and reviewer Prof. Dr. Nicolaus von Wirén Co-reviewer Prof. Dr. Gerd Weber Additional examiner Prof. Dr. Wolfgang Hanke Vice dean and head of the committee Prof. Dr. Werner Bessei Table of contents 1 Summary – Zusammenfassung ………………………......................………………………...….... 1 1.1 Summary ……………………………...........................………………………………………........ 1 1.2 Zusammenfassung ……………………........................…………………………………….......... 3 2 Introduction ………………………………………………………...…............................................... 5 2.1 Heavy metals: definition and terminology ……...………………..........……....................... 5 2.2 Metal homeostasis in higher plants: dealing with deficiency and toxicity ........................ 5 2.2.1 The physiological
    [Show full text]
  • The Role of Zip Superfamily of Metal Transporters in Chronic Diseases, Purification & Characterization of a Bacterial Zip Tr
    Wayne State University Wayne State University Theses 1-1-2011 The Role Of Zip Superfamily Of Metal Transporters In Chronic Diseases, Purification & Characterization Of A Bacterial Zip Transporter: Zupt. Iryna King Wayne State University Follow this and additional works at: http://digitalcommons.wayne.edu/oa_theses Part of the Biochemistry Commons, and the Molecular Biology Commons Recommended Citation King, Iryna, "The Role Of Zip Superfamily Of Metal Transporters In Chronic Diseases, Purification & Characterization Of A Bacterial Zip Transporter: Zupt." (2011). Wayne State University Theses. Paper 63. This Open Access Thesis is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Theses by an authorized administrator of DigitalCommons@WayneState. THE ROLE OF ZIP SUPERFAMILY OF METAL TRANSPORTERS IN CHRONIC DISEASES, PURIFICATION & CHARACTERIZATION OF A BACTERIAL ZIP TRANSPORTER: ZUPT by IRYNA KING THESIS Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE 2011 MAJOR: BIOCHEMISTRY & MOLECULAR BIOLOGY Approved by: ___________________________________ Advisor Date © COPYRIGHT BY IRYNA KING 2011 All Rights Reserved DEDICATION I dedicate this work to my father, Julian Banas, whose footsteps I indisputably followed into science & my every day inspiration, my son, William Peter King ii ACKNOWLEDGMENTS First and foremost I would like to thank the department of Biochemistry & Molecular Biology at Wayne State University School of Medicine for giving me an opportunity to conduct my research and be a part of their family. I would like to thank my advisor Dr. Bharati Mitra for taking me into the program and nurturing a biochemist in me.
    [Show full text]
  • Insulin Action/Molecular Metabolism
    INSULIN ACTION—ADIPOCYTECATEGORY BIOLOGY 1692-P 1694-P Stress in Beta Cells Obtained with Laser Capture Microdissection Biopsy-Proven Insulitis of Clinical Islet Transplantation Is Not from Cadaver Pancreases of Brain Dead Donors Reversed by Steroid Therapy AREF EBRAHIMI, MIN-HO JUNG, JONATHAN M. DREYFUSS, HUI PAN, DENNIS ANNA LAM, BEHRUZ RAHIMI, SHARLEEN IMES, KIM SOLEZ, JAMES SHAPIRO, C. SGROI, SUSAN BONNER-WEIR, GORDON C. WEIR, Boston, MA PETER A. SENIOR, Edmonton, AB, Canada Brain death of pancreas donors is thought to lead to the expression of Gradual decline in islet function remains a challenge in clinical islet infl ammatory, stress and apoptotic pathways in isolated islets resulting in transplantation (CIT), but acute graft loss is relatively uncommon. Here we poor clinical outcomes. To test this hypothesis we obtained cadaveric pan- describe a case of acute decline in graft function with histology suggesting creases from brain dead pancreatic donors (n=7, mean age 5011) and normal an immune mechanism. A 49 year old female (BMI 24.4 kg/m2, insulin 0.3 pancreatic tissue obtained at surgery done for pancreatic neoplasms (n=7, U/kg) with type 1 diabetes for 37 years underwent two CIT (6071 and 6827 age 699). Frozen sections were subjected to laser capture microdissection islet equivalents/kg) following alemtuzumab induction with tacrolimus (TAC, to obtain beta-cell rich islet tissue, from which extracted RNA was analyzed mean 8 ug/L) and mycophenolate mofetil for maintenance. Initial engraft- with Affymetrix arrays. Gene expression of the two groups was evaluated ment was reasonable (β2 score of 12 at 1 week), but β2 score gradually with principle component analysis (PCA), and differential expression anal- declined (Figure 1) rising to 19 after the second CIT.
    [Show full text]
  • The Effect of Acid on the Dynamics of Intracellular Zinc and the Marker Expressions Of
    The Effect of Acid on the Dynamics of Intracellular Zinc and the Marker Expressions of Pluripotency in Somatic Cells A thesis presented to the faculty of the College of Arts and Sciences of Ohio University In partial fulfillment of the requirements for the degree Master of Science Yuli Hu April 2021 © 2021 Yuli Hu. All Rights Reserved. 2 This thesis titled The Effect of Acid on the Dynamics of Intracellular Zinc and the Marker Expressions of Pluripotency in Somatic Cells by YULI HU has been approved for the Department of Biological Sciences and the College of Arts and Sciences by Yang V. Li Professor of Biomedical Sciences Florenz Plassmann Dean, College of Arts and Sciences 3 Abstract YULI HU, M.S., April 2021, Biological Sciences The Effect of Acid on the Dynamics of Intracellular Zinc and the Marker Expressions of Pluripotency in Somatic Cells Director of Thesis: Yang V. Li Microenvironmental pH is one of the factors that affect the stability of zinc- protein binding. The tight binding between zinc and proteins is favored by the basic pH, whereas acidic pH favors a loose bound, and treatment of strong acid results in the dissociation of zinc. Physiologically, the stomach uses a very acidic pH to digest food which results in a high amount of soluble zinc in the stomach. Whether or not zinc co- present with acid and the effect of zinc on the gastric lining has rarely been discussed. In my experiments, acidic treatment induced the expression of a pluripotent marker in primary cultured gastric cells. It also stimulated the release of intracellular zinc, suggesting that acidic pH supported protein expression through dynamic zinc regulation.
    [Show full text]
  • Universidade Federal Do Rio Grande Do Sul
    UNIVERSIDADE FEDERAL DO RIO GRANDE DO SUL CENTRO DE BIOTECNOLOGIA PROGRAMA DE PÓS-GRADUAÇÃO EM BIOLOGIA CELULAR E MOLECULAR ANÁLISE DE microRNAs-LIKE EM Cryptococcus gattii Francine Melise dos Santos Dissertação submetida ao Programa de Pós-Graduação em Biologia Celular e Molecular do Centro de Biotecnologia da Universidade Federal do Rio Grande do Sul como requisito parcial para obtenção do Grau de Mestre em Biologia Celular e Molecular. Orientador: Prof. Dr. Charley Christian Staats Co-orientadora: Profª. Drª Marilene Henning Vainstein Porto Alegre, Outubro de 2013. Este trabalho foi desenvolvido no Laboratório de Fungos de Importância Médica e Biotecnológica, situado no Centro de Biotecnologia da Universidade Federal do Rio Grande do Sul. Para seu desenvolvimento, este trabalho contou com fomento do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) e da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). 2 AGRADECIMENTOS - Ao meu orientador, Dr. Charley C. Staats, por todo apoio, incentivo, paciência e acessibilidade, que foram essenciais para criar um ambiente confortável para pesquisa e, além disso, por acreditar na minha capacidade ao longo do projeto desenvolvido e por me incluir em um projeto inovador como este; - À professora Marilene H. Vainstein, por ter me acolhido no grupo logo após minha graduação e permitir que usufruísse de toda a estrutura e conhecimento do grupo em uma área de atuação completamente diferente, o que foi essencial para meu crescimento pessoal e profissional; - Ao professor Augusto Schrank que, assim como a professora Marilene, me recebeu no grupo e possibilitou meu crescimento profissional e pessoal dentro de um grupo qualificado; - À Lívia, que sempre se mostrou envolvida com os trabalhos do grupo e disponível para solucionar problemas e dúvidas no decorrer do trabalho em laboratório, assim como sua preocupação com nosso bem-estar e, além disso, pela amizade; - Aos professores, Dr.
    [Show full text]
  • GSK-3) in Dictyostelium Discoideum and the Role of GSK-3 Binding Partners in Dictyostelium Discoideum and Mammalian Cells
    Investigation into the role of Glycogen Synthase Kinase 3 (GSK-3) in Dictyostelium discoideum and the role of GSK-3 binding partners in Dictyostelium discoideum and mammalian cells Josephine E. Forde School of Biosciences Cardiff University PhD Thesis Submitted: November 2009 UMI Number: U585B60 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Dissertation Publishing UMI U585B60 Published by ProQuest LLC 2013. Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Ca r d if f UNIVERSITY PRIFYSGOL DECLARATION C a e RD yi §> This work has not previously been accepted in substance for any degree and is not concurrently submitted in candidature for any degree. Signed ........... d & c k . - . ...................... (candidate) Date ... ! H | Q s | a o \ p .......... STATEMENT 1 This thesis is being submitted in partial fulfillment of the requirements for the degree of .................... (insert MCh, MD, MPhil, PhD etc, as appropriate) Signed .......d & 0 ( L : ...................... (candidate) Date ........... STATEMENT 2 This thesis is the result of my own independent work/investigation, except where otherwise stated. Other sources are acknowledged by explicit references. Signed d 6 < L - . ............................ (candidate) Date .
    [Show full text]
  • Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease
    REVIEW published: 22 June 2018 doi: 10.3389/fnmol.2018.00216 Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease Michelle E. Watts 1, Roger Pocock 2 and Charles Claudianos 1,3* 1Queensland Brain Institute, The University of Queensland, St. Lucia, QLD, Australia, 2Development and Stem Cells Program, Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia, 3Centre for Mental Health Research, The Australian National University, Canberra, ACT, Australia Dynamic metabolic changes occurring in neurons are critically important in directing brain plasticity and cognitive function. In other tissue types, disruptions to metabolism and the resultant changes in cellular oxidative state, such as increased reactive oxygen species (ROS) or induction of hypoxia, are associated with cellular stress. In the brain however, where drastic metabolic shifts occur to support physiological processes, subsequent changes to cellular oxidative state and induction of transcriptional sensors of oxidative stress likely play a significant role in regulating physiological neuronal function. Understanding the role of metabolism and metabolically-regulated genes in neuronal function will be critical in elucidating how cognitive functions are disrupted in pathological conditions where neuronal metabolism is affected. Here, we discuss known mechanisms regulating neuronal metabolism as well as the role of hypoxia and oxidative stress during normal and disrupted neuronal function. We also summarize recent studies implicating Edited by: a role for metabolism in regulating neuronal plasticity as an emerging neuroscience Julie A. Chowen, Hospital Infantil Universitario Niño paradigm. Jesús, Spain Keywords: oxidative metabolism, hypoxia, neurometabolism, plasticity, neurodegeneration Reviewed by: Maria Angeles Arevalo, Consejo Superior de Investigaciones INTRODUCTION Científicas (CSIC), Spain Thad A.
    [Show full text]
  • Zinc Transporters and Insulin Resistance: Therapeutic Implications
    Norouzi et al. Journal of Biomedical Science (2017) 24:87 DOI 10.1186/s12929-017-0394-0 REVIEW Open Access Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease Shaghayegh Norouzi, John Adulcikas, Sukhwinder Singh Sohal and Stephen Myers* Abstract Background: Zinc is a metal ion that is essential for growth and development, immunity, and metabolism, and therefore vital for life. Recent studies have highlighted zinc’s dynamic role as an insulin mimetic and a cellular second messenger that controls many processes associated with insulin signaling and other downstream pathways that are amendable to glycemic control. Main body: Mechanisms that contribute to the decompartmentalization of zinc and dysfunctional zinc transporter mechanisms, including zinc signaling are associated with metabolic disease, including type 2 diabetes. The actions of the proteins involved in the uptake, storage, compartmentalization and distribution of zinc in cells is under intense investigation. Of these, emerging research has highlighted a role for several zinc transporters in the initiation of zinc signaling events in cells that lead to metabolic processes associated with maintaining insulin sensitivity and thus glycemic homeostasis. Conclusion: This raises the possibility that zinc transporters could provide novel utility to be targeted experimentally and in a clinical setting to treat patients with insulin resistance and thus introduce a new class of drug target with utility for diabetes pharmacotherapy. Keywords: Zinc ions, Skeletal muscle, Cell signaling, Glycemic control Background that lead to IR will help facilitate the development of Insulin resistance (IR) is a common pathophysiological novel therapeutic strategies to prevent or lessen disease condition in which patients present with reduced insulin progression.
    [Show full text]
  • Universidade Federal De Goiás Programa De Pós-Graduação Em Medicina Tropical E Saúde Pública
    UNIVERSIDADE FEDERAL DE GOIÁS PROGRAMA DE PÓS-GRADUAÇÃO EM MEDICINA TROPICAL E SAÚDE PÚBLICA MARIELLE GARCIA SILVA ANÁLISE PROTEÔMICA DE MEMBRANAS DE Paracoccidioides sp. DURANTE PRIVAÇÃO DE ZINCO Orientadora: Dra. Célia Maria de Almeida Soares Goiânia 2014 2 UNIVERSIDADE FEDERAL DE GOIÁS PROGRAMA DE PÓS-GRADUAÇÃO EM MEDICINA TROPICAL E SAÚDE PÚBLICA MARIELLE GARCIA SILVA ANÁLISE PROTEÔMICA DE MEMBRANAS DE Paracoccidioides sp. DURANTE PRIVAÇÃO DE ZINCO Dissertação apresentada ao Programa de Pós-Graduação em Medicina Tropical e Saúde Pública da Universidade Federal de Goiás como requisito para obtenção do Título de Mestre em Medicina Tropical e Saúde Pública. Orientador: Prof. Dra. Célia Maria de Almeida Soares Goiânia 2014 ii iii Programa de Pós-Graduação em Medicina Tropical e Saúde Pública da Universidade Federal de Goiás BANCA EXAMINADORA DA DISSERTAÇÃO DE MESTRADO Aluno (a): Marielle Garcia Silva Orientador (a): Profª. Dra. Célia Maria de Almeida Soares MEMBROS Dr. Célia Maria de Almeida Soares Instituto de Ciências Biológicas, Universidade Federal de Goiás Dra. Luciana Casaletti Instituto de Ciências Biológicas, Universidade Federal de Goiás Dra. Patrícia de Sousa Lima Instituto de Ciências Biológicas, Universidade Federal de Goiás DATA: 04/08/2014 iv Dedico este trabalho ás pessoas mais importantes da minha vida... ... meus pais José e Lucélia, que sempre fizeram de tudo para me oferecer boa educação e sempre me apoiaram nas decisões tomadas. ... à minha irmã Mirelle, que sempre me ajudou nas tarefas e decisões. Obrigada pelo apoio! Se não fossem vocês, hoje não estaria onde estou! Obrigada por tudo! Amo vocês! v AGRADECIMENTOS A Deus, pela oportunidade da vida e por me abençoar a cada dia.
    [Show full text]
  • Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease
    REVIEW published: 22 June 2018 doi: 10.3389/fnmol.2018.00216 Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease Michelle E. Watts 1, Roger Pocock 2 and Charles Claudianos 1,3* 1Queensland Brain Institute, The University of Queensland, St. Lucia, QLD, Australia, 2Development and Stem Cells Program, Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia, 3Centre for Mental Health Research, The Australian National University, Canberra, ACT, Australia Dynamic metabolic changes occurring in neurons are critically important in directing brain plasticity and cognitive function. In other tissue types, disruptions to metabolism and the resultant changes in cellular oxidative state, such as increased reactive oxygen species (ROS) or induction of hypoxia, are associated with cellular stress. In the brain however, where drastic metabolic shifts occur to support physiological processes, subsequent changes to cellular oxidative state and induction of transcriptional sensors of oxidative stress likely play a significant role in regulating physiological neuronal function. Understanding the role of metabolism and metabolically-regulated genes in neuronal function will be critical in elucidating how cognitive functions are disrupted in pathological conditions where neuronal metabolism is affected. Here, we discuss known mechanisms regulating neuronal metabolism as well as the role of hypoxia and oxidative stress during normal and disrupted neuronal function. We also summarize recent studies implicating Edited by: a role for metabolism in regulating neuronal plasticity as an emerging neuroscience Julie A. Chowen, Hospital Infantil Universitario Niño paradigm. Jesús, Spain Keywords: oxidative metabolism, hypoxia, neurometabolism, plasticity, neurodegeneration Reviewed by: Maria Angeles Arevalo, Consejo Superior de Investigaciones INTRODUCTION Científicas (CSIC), Spain Thad A.
    [Show full text]