Molecular characterization of Saccharomyces cerevisiae extracellular matrix and yeast response to different sizes of hyaluronan

摘要

Yeast, Saccharomyces cerevisiae, presents itself as the best studied eukaryoticmodel, with the possibility to modify its genetic information with highly advancedmolecular techniques. This microorganism displays a high degree of similarity andconservation of processes with higher eukaryotes. Several fundamental mechanismssuch as cell cycle regulation, DNA replication, recombination and repair were firstuncovered in this microorganism. From areas as cancer to neurological diseases, asParkinson, yeast has provided vital information.Different kinds of diseases in humans are connected to the Extracellular Matrix(ECM), like fibrosis and scleroderma. Therefore, the study of ECM componentsfunction as well as its regulation has been receiving lots of attention. Several of these,such as the structural molecule Hyaluronic Acid (HA) and diffusible growth factors,have the capacity to signal and redirect the behavior of the surrounding cells. HA hasthe ability to give different signal inputs depending solely on its size and concentration.Yeast is a unicellular eukaryotic with the remarkable capacity to live asindividual, small aggregates and colonies. Within a colony, yeast cells live or dieaccording to their relative position, being able to differentiate into hyphae, as well aspseudohyphae, and stalks. All these accomplished through the communication betweenthe cells within the colony, which are embedded on a yet uncharacterized ECM.Besides ECM tridimensional structure aspect, none is known regarding itscomposition and organization. So an efficient method for the extraction, analysis andidentification of S. cerevisiae ECM components, proteins and sugars, in colonies iscurrently in the last phase of implementation. The knowledge of the main constituentsof the ECM will be a milestone in the establishment of this microbe as a modelorganism for ECM-related processes.Yeast doesn’t present the necessary enzymes and receptors to produce aresponse from HA. As yeast lacks the capacity to produce, degrade or “understand” theHA molecules, it is an excellent model for the manipulation of all aspects regarding theeukaryotic transduction of information from HA. The heterologous expression of HAreceptors in yeast (CD44 and HMMR),the effect of this glycosaminoglycan on the mainpathways, HOG, PKC or TOR, as well as changes in duplication time, chronologicalaging or life span, are also currently underway.The main asset of our work resides on the use of a simpler and better understoodmodel, the yeast, for the study of HA effects on eukaryotic cells, and how theinformation is transduced.The characterization of yeast own ECM, and the understanding of the HA effecton this microorganism could lead yeast to a privileged position as a model organism forthe study of ECM-related pathologies.