The Exocyst Complex in Health and Disease
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Investigating the Architecture and Vesicle Tethering Function of the Yeast Exocyst Complex: a Dissertation
University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2016-01-28 Investigating the Architecture and Vesicle Tethering Function of the Yeast Exocyst Complex: A Dissertation Margaret R. Heider University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Cell Biology Commons, Molecular Biology Commons, and the Structural Biology Commons Repository Citation Heider MR. (2016). Investigating the Architecture and Vesicle Tethering Function of the Yeast Exocyst Complex: A Dissertation. GSBS Dissertations and Theses. https://doi.org/10.13028/M2JG66. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/832 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. INVESTIGATING THE ARCHITECTURE AND VESICLE TETHERING FUNCTION OF THE YEAST EXOCYST COMPLEX A Dissertation Presented By MARGARET ROSE HEIDER Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester In partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY January 28, 2016 Biochemistry and Molecular Pharmacology SIGNATURE PAGE INVESTIGATING THE ARCHITECTURE AND VESICLE TETHERING FUNCTION OF THE YEAST EXOCYST COMPLEX A Dissertation -
The Role of the Exocyst in Exocytosis and Cell Migration
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Summer 2010 The Role of the Exocyst in Exocytosis and Cell Migration Jianglan Liu University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Cell Biology Commons Recommended Citation Liu, Jianglan, "The Role of the Exocyst in Exocytosis and Cell Migration" (2010). Publicly Accessible Penn Dissertations. 201. https://repository.upenn.edu/edissertations/201 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/201 For more information, please contact [email protected]. The Role of the Exocyst in Exocytosis and Cell Migration Abstract The exocyst, an evolutionarily conserved octameric protein complex, plays a crucial role in the tethering of post-Golgi secretory vesicles to the plasma membrane for exocytosis and cell migration. How the exocyst is targeted to sites of exocytosis and how this complex regulates cell migration are poorly understood. I have carried out experiments to characterize Exo70, a component of the exocyst complex. Firstly, I found that Exo70 directly interacts with phosphatidylinositol 4,5-bisphosphate through positively charged residues at its C-terminus, and this interaction is critical for the plasma membrane targeting of Exo70. Using the ts045 vesicular stomatitis virus glycoprotein trafficking assay, I found that the Exo70-lipid interaction is critical for the docking and fusion of post-Golgi secretory vesicles with the plasma membrane. Secondly, I demonstrate that the exocyst plays a pivotal role in tumor cell invasion. Invadopodia are actin-rich membrane protrusions formed by tumor cells that degrade the extracellular matrix for invasion. -
The Role of Secretory Pathways in Candida Albicans Pathogenesis
Journal of Fungi Review The Role of Secretory Pathways in Candida albicans Pathogenesis 1,2, 1, 1,3 1,3 1,2 Christiane Rollenhagen y, Sahil Mamtani y, Dakota Ma , Reva Dixit , Susan Eszterhas and Samuel A. Lee 1,2,* 1 Medicine Service, White River Junction VA Medical Center, White River Junction, VT 05009, USA; [email protected] (C.R.); [email protected] (S.M.); [email protected] (D.M.); [email protected] (R.D.); [email protected] (S.E.) 2 Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA 3 Dartmouth College, Hanover, NH 03755, USA * Correspondence: [email protected] These authors contributed equally to this work. y Received: 18 January 2020; Accepted: 20 February 2020; Published: 24 February 2020 Abstract: Candida albicans is a fungus that is a commensal organism and a member of the normal human microbiota. It has the ability to transition into an opportunistic invasive pathogen. Attributes that support pathogenesis include secretion of virulence-associated proteins, hyphal formation, and biofilm formation. These processes are supported by secretion, as defined in the broad context of membrane trafficking. In this review, we examine the role of secretory pathways in Candida virulence, with a focus on the model opportunistic fungal pathogen, Candida albicans. Keywords: Candida albicans; biofilm; filamentation; pathogenesis; secretion; trafficking; virulence 1. Introduction The fungus Candida albicans is a commensal organism and part of the human microbiome. In certain circumstances, it can become an opportunistic pathogen and has, therefore, been used as a model of fungal pathogenesis [1]. -
EXOCYST COMPLEX and ENDOCYTIC TRAFFICKING in POLARIZED EPITHELIAL CELLS by Asli Oztan Matos B.S. Bogazici University, Turkey 1
EXOCYST COMPLEX AND ENDOCYTIC TRAFFICKING IN POLARIZED EPITHELIAL CELLS by Asli Oztan Matos B.S. Bogazici University, Turkey 1997 M.S. Bilkent University, Turkey 1999 Submitted to the Graduate Faculty of The School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2007 UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE This dissertation was presented by Asli Oztan Matos It was defended on November 20th, 2007 and approved by Dr. Linton Traub Committee Chair Department of Cell Biology & Physiology Dr. Ora Weisz Department of Medicine Dr. Meir Aridor Department of Cell Biology & Physiology Dr. Adam Linstedt Department of Biological Sciences, CMU Dr. Gerard Apodaca Dissertation Advisor Department of Medicine ii EXOCYST COMPLEX AND MEMBRANE TRAFFICKING IN POLARIZED EPITHELIAL CELLS Asli Oztan Matos, M.S. The octameric exocyst complex is associated with the junctional complex and recycling endosomes, and is proposed to selectively tether cargo vesicles directed toward the basolateral surface of polarized Madin-Darby canine kidney (MDCK) cells. I observed that the exocyst subunits Sec6, Sec8, and Exo70 were localized to early endosomes, transferrin-positive common recycling endosomes, and Rab11a-positive apical recycling endosomes of polarized MDCK cells. Consistent with its localization to multiple populations of endosomes, addition of function-blocking Sec8 antibodies to streptolysin- O permeabilized cells revealed exocyst requirements for several endocytic pathways including basolateral recycling, apical recycling, and basolateral-to-apical transcytosis. The latter was selectively dependent on interactions between the small GTPase Rab11a and Sec15A and was inhibited by the expression of the C-terminus of Sec15A or downregulation of Sec15A expression using shRNA. -
Directing Angiogenesis: Cellular Responses to Gradients in Vitro
All you need is love List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals. I Barkefors, I., Le Jan, S., Jakobsson, L., Hejll, E., Carlson, G., Johansson, H., Jarvius, J., Park, J. W., Jeon, N. L., Kreuger, J., (2008). J. Biol. Chem., 283(20):13905–13912. II Barkefors, I., Thorslund, S., Nikolajeff, F., Kreuger, J., (2009). A fluidic device to study directional angiogenesis in complex tissue and organ culture models. Lab Chip, 9(4):529-535. III Barkefors, I., Fuchs, P. F., Bergström, T., Heldin, J., Nilsson, K. F., Kreuger, J., (2010). EXOC3l2 associates with the exocyst complex and mediates directional migration of endothelial cells. Submitted. Reprints were made with permission from the respective publishers. Contents INTRODUCTION ..................................................................................................11 CELL MIGRATION ..................................................................................................11 A sense of direction ........................................................................................13 Matrix interactions .........................................................................................15 The role of the exocyst complex in cell polarization .....................................16 Exocyst composition and localization .....................................................................16 Migration and polarization ......................................................................................18