DOCSLIB.ORG

Role of Caveolin-3 and Caveolae Mechanics in Muscle Pathophysiology Melissa Dewulf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Role of Caveolin-3 and Caveolae Mechanics in Muscle Pathophysiology Melissa Dewulf Role of caveolin-3 and caveolae mechanics in muscle pathophysiology Melissa Dewulf To cite this version: Melissa Dewulf. Role of caveolin-3 and caveolae mechanics in muscle pathophysiology. Cellular Biol- ogy. Université Paris-Saclay, 2018. English. NNT : 2018SACLS067. tel-02145218 HAL Id: tel-02145218 https://tel.archives-ouvertes.fr/tel-02145218 Submitted on 2 Jun 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Thèse de doctorat de l'Université Paris-Saclay préparée à l’Université Paris-Saclay École doctorale n°568 Signalisations et réseaux intégratifs en biologie (Biosigne) Spécialité de doctorat: Biologie cellulaire et moléculaire Thèse présentée et soutenue à Paris, le 29 mars 2018, par Melissa Dewulf Role of caveolin-3 and caveolae mechanics in the muscle pathophysiology Composition du Jury : Pr. Karim Benihoud Président du jury Dr. Soazig Le lay Rapporteur Dr. Edgar Gomes Rapporteur Dr. Julie Dam Examinateur Dr. Stéphane Vassilopoulos Examinateur Dr. Christophe Lamaze Directeur de thèse ! ! ! ! ! ! ! « Et voilà, on a les droits ! » François Pignon Acknowledgements The last four years were probably the most challenging but also the most exciting of my life, and it is time for me to thank many people who were involved, in so many different ways, in this adventure. I will take this opportunity to address my first words to my supervisor. Christophe, thank you so much for trusting me with this project, which was not always easy, but you were always very optimistic and in the end, I believe we made it work! You have always been very supportive concerning the choices I made for my project, but also concerning my “extra- research” projects, which I particularly appreciated. At the personal level, you are a man of all the extremes, extremely scandalous, but also extremely interesting and funny! You are a “personnage haut en couleurs” as we would say in French, and I am very happy Graça put me on your way. I would like now to mention the other person “qui tire les ficelles”. Cédric, I am so grateful that you are such a nice and patient person! I think we can say that we have different standards of organization, clumsiness and the list could go on for a while, but it worked anyway! It probably has to do with the fact that we also share many different interests, food being the most important one, but we cannot exclude that science was also part of the game… You have been a great teacher and thanks to you, I have now quite a list of skills, both useful for the experiments and for trying to do nice illustrations, that I can brag about to a very limited amount of people, but still…Finally, thank you for all the time you invested in making sure my manuscript would be as perfect as possible while you were preparing yourself for the famous concours. I would also like to thank Ludger who would always bring precious feedbacks whenever I would be on stage during our weekly labmeetings. I am also very grateful for your trust with the organization of the unit retreat and different team building events, I enjoyed it a lot! I would like now to warmly thank Dr Soazig Le lay and Dr Edgar Gomes for the time they dedicated to review my manuscript and the nice and pertinent feedback they gave me. I would also like to address a few words to Dr Stéphane Vassilopoulos who I have met a few years ago and who I always enjoyed having animated scientific discussions with. I am thus very happy that he accepted to evaluate my work. I would also like to thank Pr Karim Benihoud who was my PhD tutor and will preside over my thesis jury, and Dr Julie Dam for kindly accepting my invitation. This work wouldn’t have been possible without our collaborators from the Institut de myologie. In addition to Stéphane that I mentioned before, I would like to thank Gillian Butler-Browne for the scientific discussion and support on this project, Anne Bigot who generated all the muscle cell lines we used for our work and who has always been available for advices. Finally, I thank Catherine Coirault who trained and advised me on the use of the Flexcell device, and who also was one of my thesis tutors. Part of the work has also been done through collaborations within our unit. Valérie and Christine, thank you for the precious time you dedicated to reveal the dirty secrets of my cells, our paper looks much more fancy now thanks to you! To me, a good thesis requires a good scientific and human environment, and regarding this, I have been very lucky. The Lamaze and Johannes teams are a melting pot of people, each of them with its own little hint of craziness, and I will definitely remember having a great time and laughing a lot! First, Nicolas, who actually asked me to mention him first, has been my perfect sidekick during this thesis. Although I have never been supportive of his sense of humor, I really hope I have actually been as supportive for everything else as he has been with me during these last four years. PhD sidekicks actually come in different flavors: Carlos, thank you for being you, so annoying and so great at the same time! And Thomas, thank you for always being present whenever I need to tell a story, complain, or just drink a coffee on the terrace, no matter the weather… For great discussions, scientific or others, I could also always count on Cédric, Christine, Estelle, Valérie or Massi! I will always remember Cédric’s enthusiasm for the construction of a new stretcher device with a 3D printer or for the discovery of the saucisson paradise, our games of “which emoji movie am I?”, the long series of quotes from Le diner de con, and we should not forget about our 80’s aerobic moments with Christine, our endless talks on life with Valérie, our mutual teasing with Estelle and our daily rendez-vous with Massi at his bench to do a summary of our day. I will of course remember all of our big laughs, sushi a volonté parties, and many coffee breaks and lunches that are perfect times to talk about anything that crosses our minds. More recently, we got to see many new faces arriving, which fortunately allowed me to expand the number of great people I met during my time in the lab. Satish with his wisdom and his great repartee that makes me laugh so much, Manon la force tranquille with her calm and patience, although as we say in French “il faut se méfier de l’eau qui dort” and our very own tornado Alison who, together with Ewan, brought us a very nice British (and neapolitan) ambiance to our daily life. This is without forgetting about past members of the lab who left us with nice memories. Ma ptite Steph, who has always been a great support and who I shared so much with. Natacha, Weiwei, Henri, Daniela, whose names we can still come across when using old pipetboys or tube racks, as if they never left. I would also like to thank all of the members of the Lamaze and Johannes team, as scientific and non-scientific support was something I could find very easily between the walls that we share. Beyond these walls, I got to meet many other different people, who for some of them became very good friends. Fortunately, I started this adventure in Curie with Léa, with the two other members of the bras cassés, Arthur and Maxence who were never too far away from us. Since university, we were always there to support each other through every single step of the process and I am so happy we got to share all of this together! Léa and Arthur were leading the dance, showing us the way on the road of excellency, while Mikou would always be there to share with us his latest discovery while drinking and spilling beer everywhere. Léa, knowing that your were there, just 5 floors away, made everything easier for me and as we were both trying to make our way into the life of the institute by attending a young scientist retreat, we got to meet the people who would become our good friends. Suddenly, it made me feel like I was going back to school again and I would get to see my friends every day. Camilla is this very calm, precise, and loving person that anyone should have in his life. Luckily for me, since then, she never left me and I am so grateful that she allowed me to integrate her fully in my professional and especially personal life, as I would be completely lost if she ever decided to leave it. She is the definition of a good friend and I am so glad I can count on her for anything. Imène is in the category of person that might seem a little bit inaccessible at first, but it is so worth it to scratch the surface a little, and I am already missing so much our long brainstormings about life and science.
Load more

Recommended publications
  • Microanatomy of Muscles
    Microanatomy of Muscles Anatomy & Physiology Class Three Main Muscle Types Objectives: By the end of this presentation you will have the information to: 1. Describe the 3 main types of muscles. 2. Detail the functions of the muscle system. 3. Correctly label the parts of a myocyte (muscle cell) 4. Identify the levels of organization in a skeletal muscle from organ to myosin. 5. Explain how a muscle contracts utilizing the correct terminology of the sliding filament theory. 6. Contrast and compare cardiac and smooth muscle with skeletal muscle. Major Functions: Muscle System 1. Moving the skeletal system and posture. 2. Passing food through the digestive system & constriction of other internal organs. 3. Production of body heat. 4. Pumping the blood throughout the body. 5. Communication - writing and verbal Specialized Cells (Myocytes) ~ Contractile Cells Can shorten along one or more planes because of specialized cell membrane (sarcolemma) and specialized cytoskeleton. Specialized Structures found in Myocytes Sarcolemma: The cell membrane of a muscle cell Transverse tubule: a tubular invagination of the sarcolemma of skeletal or cardiac muscle fibers that surrounds myofibrils; involved in transmitting the action potential from the sarcolemma to the interior of the myofibril. Sarcoplasmic Reticulum: The special type of smooth endoplasmic Myofibrils: reticulum found in smooth and a contractile fibril of skeletal muscle, composed striated muscle fibers whose function mainly of actin and myosin is to store and release calcium ions. Multiple Nuclei (skeletal) & many mitochondria Skeletal Muscle - Microscopic Anatomy A whole skeletal muscle (such as the biceps brachii) is considered an organ of the muscular system. Each organ consists of skeletal muscle tissue, connective tissue, nerve tissue, and blood or vascular tissue.
    [Show full text]
  • Mea6 Controls VLDL Transport Through the Coordinated Regulation of COPII Assembly
    Cell Research (2016) 26:787-804. npg © 2016 IBCB, SIBS, CAS All rights reserved 1001-0602/16 $ 32.00 ORIGINAL ARTICLE www.nature.com/cr Mea6 controls VLDL transport through the coordinated regulation of COPII assembly Yaqing Wang1, *, Liang Liu1, 2, *, Hongsheng Zhang1, 2, Junwan Fan1, 2, Feng Zhang1, 2, Mei Yu3, Lei Shi1, Lin Yang1, Sin Man Lam1, Huimin Wang4, Xiaowei Chen4, Yingchun Wang1, Fei Gao5, Guanghou Shui1, Zhiheng Xu1, 6 1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; 2University of Chinese Academy of Sciences, Beijing 100101, China; 3School of Life Science, Shandong University, Jinan 250100, China; 4Institute of Molecular Medicine, Peking University, Beijing 100871, China; 5State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; 6Translation- al Medical Center for Stem Cell Therapy, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China Lipid accumulation, which may be caused by the disturbance in very low density lipoprotein (VLDL) secretion in the liver, can lead to fatty liver disease. VLDL is synthesized in endoplasmic reticulum (ER) and transported to Golgi apparatus for secretion into plasma. However, the underlying molecular mechanism for VLDL transport is still poor- ly understood. Here we show that hepatocyte-specific deletion of meningioma-expressed antigen 6 (Mea6)/cutaneous T cell lymphoma-associated antigen 5C (cTAGE5C) leads to severe fatty liver and hypolipemia in mice. Quantitative lip- idomic and proteomic analyses indicate that Mea6/cTAGE5 deletion impairs the secretion of different types of lipids and proteins, including VLDL, from the liver.
    [Show full text]
  • Abl Family Tyrosine Kinases Govern Igg Extravasation in the Skin in a Murine Pemphigus Model
    ARTICLE https://doi.org/10.1038/s41467-019-12232-3 OPEN Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model Sachiko Ono1, Gyohei Egawa1, Takashi Nomura1, Akihiko Kitoh1, Teruki Dainichi 1, Atsushi Otsuka1, Saeko Nakajima1, Masayuki Amagai2, Fumi Matsumoto3, Mami Yamamoto 3, Yoshiaki Kubota4, Toshiyuki Takai5, Tetsuya Honda1 & Kenji Kabashima 1,6 1234567890():,; The pathway of homeostatic IgG extravasation is not fully understood, in spite of its importance for the maintenance of host immunity, the management of autoantibody- mediated disorders, and the use of antibody-based biologics. Here we show in a murine model of pemphigus, a prototypic cutaneous autoantibody-mediated disorder, that blood- circulating IgG extravasates into the skin in a time- and dose-dependent manner under homeostatic conditions. This IgG extravasation is unaffected by depletion of Fcγ receptors, but is largely attenuated by specific ablation of dynamin-dependent endocytic vesicle for- mation in blood endothelial cells (BECs). Among dynamin-dependent endocytic vesicles, IgG co-localizes well with caveolae in cultured BECs. An Abl family tyrosine kinase inhibitor imatinib, which reduces caveolae-mediated endocytosis, impairs IgG extravasation in the skin and attenuates the murine pemphigus manifestations. Our study highlights the kinetics of IgG extravasation in vivo, which might be a clue to understand the pathological mechanism of autoantibody-mediated autoimmune disorders. 1 Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 2 Department of Dermatology, Keio University Graduate School of Medicine, Tokyo, Japan. 3 Research Unit/Immunology & Inflammation, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan. 4 Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
    [Show full text]
  • Functions of Vertebrate Ferlins
    cells Review Functions of Vertebrate Ferlins Anna V. Bulankina 1 and Sven Thoms 2,* 1 Department of Internal Medicine 1, Goethe University Hospital Frankfurt, 60590 Frankfurt, Germany; [email protected] 2 Department of Child and Adolescent Health, University Medical Center Göttingen, 37075 Göttingen, Germany * Correspondence: [email protected] Received: 27 January 2020; Accepted: 20 February 2020; Published: 25 February 2020 Abstract: Ferlins are multiple-C2-domain proteins involved in Ca2+-triggered membrane dynamics within the secretory, endocytic and lysosomal pathways. In bony vertebrates there are six ferlin genes encoding, in humans, dysferlin, otoferlin, myoferlin, Fer1L5 and 6 and the long noncoding RNA Fer1L4. Mutations in DYSF (dysferlin) can cause a range of muscle diseases with various clinical manifestations collectively known as dysferlinopathies, including limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy. A mutation in MYOF (myoferlin) was linked to a muscular dystrophy accompanied by cardiomyopathy. Mutations in OTOF (otoferlin) can be the cause of nonsyndromic deafness DFNB9. Dysregulated expression of any human ferlin may be associated with development of cancer. This review provides a detailed description of functions of the vertebrate ferlins with a focus on muscle ferlins and discusses the mechanisms leading to disease development. Keywords: dysferlin; myoferlin; otoferlin; C2 domain; calcium-sensor; muscular dystrophy; dysferlinopathy; limb girdle muscular dystrophy type 2B (LGMD2B), membrane repair; T-tubule system; DFNB9 1. Introduction Ferlins belong to the superfamily of proteins with multiple C2 domains (MC2D) that share common functions in tethering membrane-bound organelles or recruiting proteins to cellular membranes. Ferlins are described as calcium ions (Ca2+)-sensors for vesicular trafficking capable of sculpturing membranes [1–3].
    [Show full text]
  • The Mir-199–Dynamin Regulatory Axis Controls Receptor-Mediated Endocytosis Juan F
    © 2015. Published by The Company of Biologists Ltd | Journal of Cell Science (2015) 128, 3197-3209 doi:10.1242/jcs.165233 RESEARCH ARTICLE The miR-199–dynamin regulatory axis controls receptor-mediated endocytosis Juan F. Aranda1,2, Alberto Canfrán-Duque1,2, Leigh Goedeke1,2, Yajaira Suárez1,2 and Carlos Fernández-Hernando1,2,* ABSTRACT mechanism for the selective uptake of essential nutrients such as Small non-coding RNAs (microRNAs) are important regulators of low-density lipoprotein (LDL), through the LDL receptor (LDLR) gene expression that modulate many physiological processes; (Brown and Goldstein, 1986), or iron, through transferrin receptor however, their role in regulating intracellular transport remains (TfR) (Harding et al., 1983). Thus, factors that affect RME have a largely unknown. Intriguingly, we found that the dynamin (DNM) direct effect on these receptors, and, in the case of LDLR, to regulate genes, a GTPase family of proteins responsible for endocytosis in intracellular cholesterol levels. In both the LDLR and TfR eukaryotic cells, encode the conserved miR-199a and miR-199b internalization processes, clathrin plays a key role during the family of miRNAs within their intronic sequences. Here, we formation of coated vesicles (Moore et al., 1987). Once vesicles are demonstrate that miR-199a and miR-199b regulate endocytic internalized, their passage through a broad endosomal compartment transport by controlling the expression of important mediators of system is required; first they are rapidly transported into early endocytosis such as clathrin heavy chain (CLTC), Rab5A, low- endosomes, where Rab5A is a key regulator (Nielsen et al., 1999), density lipoprotein receptor (LDLR) and caveolin-1 (Cav-1).
    [Show full text]
  • Mechanisms of Synaptic Plasticity Mediated by Clathrin Adaptor-Protein Complexes 1 and 2 in Mice
    Mechanisms of synaptic plasticity mediated by Clathrin Adaptor-protein complexes 1 and 2 in mice Dissertation for the award of the degree “Doctor rerum naturalium” at the Georg-August-University Göttingen within the doctoral program “Molecular Biology of Cells” of the Georg-August University School of Science (GAUSS) Submitted by Ratnakar Mishra Born in Birpur, Bihar, India Göttingen, Germany 2019 1 Members of the Thesis Committee Prof. Dr. Peter Schu Institute for Cellular Biochemistry, (Supervisor and first referee) University Medical Center Göttingen, Germany Dr. Hans Dieter Schmitt Neurobiology, Max Planck Institute (Second referee) for Biophysical Chemistry, Göttingen, Germany Prof. Dr. med. Thomas A. Bayer Division of Molecular Psychiatry, University Medical Center, Göttingen, Germany Additional Members of the Examination Board Prof. Dr. Silvio O. Rizzoli Department of Neuro-and Sensory Physiology, University Medical Center Göttingen, Germany Dr. Roland Dosch Institute of Developmental Biochemistry, University Medical Center Göttingen, Germany Prof. Dr. med. Martin Oppermann Institute of Cellular and Molecular Immunology, University Medical Center, Göttingen, Germany Date of oral examination: 14th may 2019 2 Table of Contents List of abbreviations ................................................................................. 5 Abstract ................................................................................................... 7 Chapter 1: Introduction ............................................................................
    [Show full text]
  • Caveolin-1 Is Down-Regulated in Alveolar Rhabdomyosarcomas and Negatively Regulates Tumor Growth
    www.impactjournals.com/oncotarget/ Oncotarget, Vol. 5, No. 20 Caveolin-1 is down-regulated in alveolar rhabdomyosarcomas and negatively regulates tumor growth Juan Huertas-Martínez1, Santiago Rello-Varona1, David Herrero-Martín1, Ignasi Barrau1, Silvia García-Monclús1, Miguel Sáinz-Jaspeado1, Laura Lagares-Tena1, Yaiza Núñez-Álvarez5, Silvia Mateo-Lozano2, Jaume Mora2, Josep Roma3, Nuria Toran3, Sebastian Moran4, Roser López-Alemany1, Soledad Gallego3, Manel Esteller4, Miguel A. Peinado5, Xavier García del Muro1 and Oscar M. Tirado1 1 Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain 2 Developmental Tumor Biology Laboratory, Hospital Sant Joan de Deu, Barcelona, Spain 3 Biomedical Research Unit, Hospital Universitari Vall d’Hebron, Barcelona, Spain 4 Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’ Hospitalet de Llobregat, Barcelona, Spain 5 Institut de Medicina Predictiva i Personalitzada del Càncer, Badalona, Barcelona, Spain Correspondence to: Oscar M. Tirado, email: [email protected] Keywords: alveolar rhabdomyosarcoma, Caveolin-1, muscular differentiation, 5-AZA-2’-deoxycytidine, epigenetics, cell death Received: June 26, 2014 Accepted: August 26, 2014 Published: August 27, 2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with histological variant of rhabdomyosarcoma known as alveolar rhabdomyosarcoma (ARMS) have a 5-year survival of less than 30%. Caveolin-1 (CAV1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signaling.
    [Show full text]
  • Back-To-Basics: the Intricacies of Muscle Contraction
    Back-to- MIOTA Basics: The CONFERENCE OCTOBER 11, Intricacies 2019 CHERI RAMIREZ, MS, of Muscle OTRL Contraction OBJECTIVES: 1.Review the anatomical structure of a skeletal muscle. 2.Review and understand the process and relationship between skeletal muscle contraction with the vital components of the nervous system, endocrine system, and skeletal system. 3.Review the basic similarities and differences between skeletal muscle tissue, smooth muscle tissue, and cardiac muscle tissue. 4.Review the names, locations, origins, and insertions of the skeletal muscles found in the human body. 5.Apply the information learned to enhance clinical practice and understanding of the intricacies and complexity of the skeletal muscle system. 6.Apply the information learned to further educate clients on the importance of skeletal muscle movement, posture, and coordination in the process of rehabilitation, healing, and functional return. 1. Epithelial Four Basic Tissue Categories 2. Muscle 3. Nervous 4. Connective A. Loose Connective B. Bone C. Cartilage D. Blood Introduction There are 3 types of muscle tissue in the muscular system: . Skeletal muscle: Attached to bones of skeleton. Voluntary. Striated. Tubular shape. Cardiac muscle: Makes up most of the wall of the heart. Involuntary. Striated with intercalated discs. Branched shape. Smooth muscle: Found in walls of internal organs and walls of vascular system. Involuntary. Non-striated. Spindle shape. 4 Structure of a Skeletal Muscle Skeletal Muscles: Skeletal muscles are composed of: • Skeletal muscle tissue • Nervous tissue • Blood • Connective tissues 5 Connective Tissue Coverings Connective tissue coverings over skeletal muscles: .Fascia .Tendons .Aponeuroses 6 Fascia: Definition: Layers of dense connective tissue that separates muscle from adjacent muscles, by surrounding each muscle belly.
    [Show full text]
  • Palmitoylation of Caveolin-1 and Its Importance for Structural and Functional Plasticity
    Palmitoylation of Caveolin-1 and its importance for structural and functional plasticity A DISSERTATION SUBMITTED TO THE FACULTY OF UNIVERSITY OF MINNESOTA BY Katherine R. Tonn IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY Paul G. Mermelstein November 2018 © Katherine R. Tonn Eisinger 2018 Acknowledgments I would like to thank my adviser, Dr. Paul Mermelstein, for his mentorship, training, support, and scientific flexibility. Infinite thanks to past and present members of the Mermelstein and Meisel Labs, especially Dr. Brittni Peterson, Dr. Kelsey Moore, Dr. Laura Been, Dr. Luis Martinez, Dr. Valerie Hedges, and Dr. John Meitzen, for being a source of scientific inspiration and friendship. I could not have asked for a better friend and lab colleague than Dr. Kellie Gross, whose input has kept me sane and made me a better scientist. Thanks also to stellar undergrads Kerry Trotter, Julia Dworsky, and Sam Swanson for their help and energy. Thanks to the many people who collaborated or helped in some way on the experiments presented in this thesis, including Dr. Mark Thomas, Dr. Lorene Lanier, Dr. Mark Dell’Acqua, Dr. Kevin Woolfrey, Dr. Brian Head, Dr. Jing Tong, and Dr. John Meitzen. In particular, I am extremely grateful for the collaboration of Dr. Lorene Lanier, whose enthusiasm helped reinvigorate me and this project. Finally, thanks to the members of my thesis committee, Drs. Harry Orr, Timothy Ebner, Anna Lee, and Robert Meisel, for their encouragement and guidance. i Dedication For Mom, my first and most important example of what it is to be smart, versatile, and kind.
    [Show full text]
  • Role of Stromal Caveolin-1 (CAV1) Levels in Breast Cancer Angiogenesis
    Universidad Autónoma de Madrid Programa de Doctorado en Biociencias Moleculares Role of stromal Caveolin-1 (CAV1) levels in breast cancer angiogenesis Alberto Díez Sánchez Madrid, 2018 0 1 Departamento de Bioquímica Facultad de Medicina Universidad Autónoma de Madrid Role of stromal Caveolin-1 (CAV1) levels in breast cancer angiogenesis Doctorando: Alberto Díez Sánchez, Licenciado en Biotecnología Director: Miguel Ángel del Pozo Barriuso, MD, PhD. Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) Madrid, 2018 1 2 CERTIFICADO DEL DIRECTOR DE TESIS El doctor Miguel Ángel del Pozo Barriuso CERTIFICA que el doctorando Alberto Díez Sánchez ha desarrollado y concluido su trabajo de tesis doctoral “Role of stromal Caveolin-1 (CAV1) levels in breast cancer angiogenesis” bajo su supervisión, en el Centro Nacional de Investigaciones Cardiovasculares (CNIC). Y para que así conste lo firma en Madrid, a 10 de Julio de 2018, Fdo. Dr. Miguel Ángel del Pozo Barriuso Centro Nacional de Investigaciones Cardiovasculares (CNIC) 3 4 ACKNOWLEDGMENTS It is said that scientific knowledge is built on top of the shoulder of giants, in more practical terms, I consider all these people below my personal giants. First ones I encountered, were my parents and grandparents, everything I have achieved has been done on top of their previous efforts, to them I dedicate my most sincere gratitude for teaching this once lazy kid the value of effort. Next, I have to thank all those high-school teachers and university professors that during my education have been able to spark in me the sense of amazement derived from understanding how nature works.
    [Show full text]
  • Single-Cell Analysis Uncovers Fibroblast Heterogeneity
    ARTICLE https://doi.org/10.1038/s41467-020-17740-1 OPEN Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination ✉ Lars Muhl 1,2 , Guillem Genové 1,2, Stefanos Leptidis 1,2, Jianping Liu 1,2, Liqun He3,4, Giuseppe Mocci1,2, Ying Sun4, Sonja Gustafsson1,2, Byambajav Buyandelger1,2, Indira V. Chivukula1,2, Åsa Segerstolpe1,2,5, Elisabeth Raschperger1,2, Emil M. Hansson1,2, Johan L. M. Björkegren 1,2,6, Xiao-Rong Peng7, ✉ Michael Vanlandewijck1,2,4, Urban Lendahl1,8 & Christer Betsholtz 1,2,4 1234567890():,; Many important cell types in adult vertebrates have a mesenchymal origin, including fibro- blasts and vascular mural cells. Although their biological importance is undisputed, the level of mesenchymal cell heterogeneity within and between organs, while appreciated, has not been analyzed in detail. Here, we compare single-cell transcriptional profiles of fibroblasts and vascular mural cells across four murine muscular organs: heart, skeletal muscle, intestine and bladder. We reveal gene expression signatures that demarcate fibroblasts from mural cells and provide molecular signatures for cell subtype identification. We observe striking inter- and intra-organ heterogeneity amongst the fibroblasts, primarily reflecting differences in the expression of extracellular matrix components. Fibroblast subtypes localize to discrete anatomical positions offering novel predictions about physiological function(s) and regulatory signaling circuits. Our data shed new light on the diversity of poorly defined classes of cells and provide a foundation for improved understanding of their roles in physiological and pathological processes. 1 Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre, Blickagången 6, SE-14157 Huddinge, Sweden.
    [Show full text]
  • ER-To-Golgi Trafficking and Its Implication in Neurological Diseases
    cells Review ER-to-Golgi Trafficking and Its Implication in Neurological Diseases 1,2, 1,2 1,2, Bo Wang y, Katherine R. Stanford and Mondira Kundu * 1 Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; [email protected] (B.W.); [email protected] (K.R.S.) 2 Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA * Correspondence: [email protected]; Tel.: +1-901-595-6048 Present address: School of Life Sciences, Xiamen University, Xiamen 361102, China. y Received: 21 November 2019; Accepted: 7 February 2020; Published: 11 February 2020 Abstract: Membrane and secretory proteins are essential for almost every aspect of cellular function. These proteins are incorporated into ER-derived carriers and transported to the Golgi before being sorted for delivery to their final destination. Although ER-to-Golgi trafficking is highly conserved among eukaryotes, several layers of complexity have been added to meet the increased demands of complex cell types in metazoans. The specialized morphology of neurons and the necessity for precise spatiotemporal control over membrane and secretory protein localization and function make them particularly vulnerable to defects in trafficking. This review summarizes the general mechanisms involved in ER-to-Golgi trafficking and highlights mutations in genes affecting this process, which are associated with neurological diseases in humans. Keywords: COPII trafficking; endoplasmic reticulum; Golgi apparatus; neurological disease 1. Overview Approximately one-third of all proteins encoded by the mammalian genome are exported from the endoplasmic reticulum (ER) and transported to the Golgi apparatus, where they are sorted for delivery to their final destination in membrane compartments or secretory vesicles [1].
    [Show full text]