Cecilia D'Alessio

Cecilia D'Alessio
Universidad de Buenos Aires | UBA · Department of Physiology, Molecular and Cellular Biology

Doctor

About

38
Publications
4,128
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Introduction
In the lab we are interested on understanding the molecular basis of Congenital Disorders of Glycosylation. We use fission yeast mutants as a model organism and focus on basic cell glycobiology underlying processes of the diseases. In particular, we focus in N-glycosylation and in the early steps of N-glycan processing. We also use different yeasts to express recombinant proteins, and we engineere yeast to use in bioremediation processes
Additional affiliations
March 2019 - present
Universidad de Buenos Aires
Position
  • Professor
January 2003 - present
National Research Council, Argentine
Position
  • Researcher
January 2003 - February 2019
Universidad de Buenos Aires
Position
  • Instructor

Publications

Publications (38)
Article
Full-text available
The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate to develop effective COVID-19 vaccines since it can induce potent neutralizing antibodies. We have previously reported the highly efficient production of RBD in Pichia pastoris , which is structurally similar to the same protein produced in mammalian HEK...
Article
Full-text available
Congenital disorders of glycosylation type I (CDG-I) are inherited human diseases caused by deficiencies in lipid-linked oligosaccharide (LLO) synthesis or the glycan transfer to proteins during N-glycosylation. We constructed a platform of 16 Schizosaccharomyces pombe strains that synthesize all possible theoretical combinations of LLOs containing...
Preprint
Full-text available
We covalently coupled the RBD domain of SARS-CoV-2 produced in Pichia pastoris to a decameric carrier to produce a potent immunogen
Preprint
Since the discovery of SARS-CoV-2, several antigens have been proposed to be part of COVID-19 vaccines. The receptor binding domain (RBD) of Spike protein is one of the promising candidates to develop effective vaccines since it can induce potent neutralizing antibodies. We previously reported the production of RBD in Pichia pastoris and showed it...
Article
Full-text available
The yeast Pichia pastoris is a cost-effective and easily scalable system for recombinant protein production. In this work we compared the conformation of the receptor binding domain (RBD) from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Spike protein expressed in P. pastoris and in the well established HEK-293T mammalian cell syste...
Preprint
Full-text available
The yeast Pichia pastoris is a cost-effective and easily scalable system for recombinant protein production. In this work we compared the conformation of the receptor binding domain (RBD) from SARS-CoV-2 Spike protein expressed in P. pastoris and in the well established HEK-293T mammalian cell system. RBD obtained from both yeast and mammalian cell...
Article
Full-text available
Glucosidase I (GI) removes the outermost glucose from protein-linked Glc3Man9GlcNAc2 (G3M9) in the endoplasmic reticulum (ER). Individuals with congenital disorders of glycosylation MOGS-CDG bear mutations in the GI encoding-gene (gls1). Although GI absence has been reported to produce lethality in Schizosaccharomyces pombe yeasts, here we obtained...
Article
Full-text available
Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion of cytoplasmic components. Here we report that a novel Drosophila immunophilin, which we have named Zonda, is critically required for starvation-induced autophagy. We show that Zonda operates at early stages of the process, specifically for Vps34-mediate...
Article
Full-text available
UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). According to a bioinformatics search there are...
Article
Full-text available
Culex pipiens is the most cosmopolitan mosquito of the Pipiens Assemblage. By studying the nature of interactions between this species and microorganisms common to its breeding environment we can unravel important pitfalls encountered during development. We tested the survival rate of larval stages, pupae and adults of a Cx. pipiens colony exposed...
Article
The N-glycan-dependent quality control of glycoprotein folding prevents endoplasmic reticulum (ER) to Golgi exit of folding intermediates, irreparably misfolded glycoproteins, and incompletely assembled multimeric complexes. It also enhances folding efficiency by preventing aggregation and facilitating formation of proper disulfide bonds. The contr...
Article
Full-text available
N-glycans are modified as part of a quality control mechanism during glycoprotein folding in the endoplasmic reticulum (ER). Glucosidase II (GII) plays a critical role by generating monoglucosylated glycans that are recognized by lectin-chaperones, calnexin and calreticulin. To understand how the hydrolytic activity of GIIα is enhanced by the manno...
Article
Full-text available
UDP-glucose: glycoprotein glucosyltransferase (UGGT) is a key player in the quality control mechanism (ER-QC) that newly synthesized glycoproteins undergo in the ER. It has been shown that the UGGT Arabidopsis orthologue is involved in ER-QC; however, its role in plant physiology remains unclear. Here, we show that two mutant alleles in the At1g712...
Article
Full-text available
N-glycosylation in the endoplasmic reticulum (ER) consists of the transfer of a preassembled glycan conserved among species (Glc3Man9GlcNAc2) from a lipid donor to a consensus sequence within a nascent protein that is entering the ER. The protein-linked glycans are then processed by glycosidases and glycosyltransferases in the ER producing specific...
Article
Full-text available
Protein aggregation is linked to more than 30 human pathologies, including Alzheimer's and Parkinson's diseases. Since small oligomers that form at the beginning of the fibrillation process probably are the most toxic elements, therapeutic strategies involving fibril fragmentation could be detrimental. An alternative approach, named kinetic inhibit...
Chapter
Full-text available
Almost one-third of proteins synthesized by eukaryotic cells belong to the secretory pathway, entering the endoplasmic reticulum (ER) either co- or posttranslationally. In the ER, proteins acquire their native tertiary fold, disulfide bonds are formed, and in some cases, they assemble into oligomeric structures. Numerous folding-assisting enzymes a...
Article
Full-text available
Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases (CDKs). Activation of the cyclin B-cdc2 kinase complex is a pivotal step in mitotic initiation and the tyrosine kinase Wee1 is a key regulator of cell cycle sequence during G2/M transition and inhibits mitotic entry by phospho...
Article
Full-text available
Here we report for the first time the three-dimensional structure of a mannose 6-phosphate receptor homology (MRH) domain present in a protein with enzymatic activity, glucosidase II (GII). GII is involved in glycoprotein folding in the endoplasmic reticulum. GII removes the two innermost glucose residues from the Glc3Man9GlcNAc2 transferred to nas...
Article
Full-text available
Glucosidase II (GII) sequentially removes the two innermost glucose residues from the glycan (Glc(3)Man(9)GlcNAc(2)) transferred to proteins. GII also participates in cycles involving the lectin/chaperones calnexin (CNX) and calreticulin (CRT) as it removes the single glucose unit added to folding intermediates and misfolded glycoproteins by the UD...
Article
The N-glycan-dependent quality control of glycoprotein folding prevents endoplasmic to Golgi exit of folding intermediates, irreparably misfolded glycoproteins and incompletely assembled multimeric complexes. It also enhances folding efficiency by preventing aggregation and facilitating formation of proper disulfide bonds. The control mechanism ess...
Article
Full-text available
Glucosidase II (GII) plays a key role in glycoprotein biogenesis in the endoplasmic reticulum (ER). It is responsible for the sequential removal of the two innermost glucose residues from the glycan (Glc(3)Man(9)GlcNAc(2)) transferred to Asn residues in proteins. GII participates in the calnexin/calreticulin cycle; it removes the single glucose uni...
Article
Full-text available
Glucosidase II, one of the early N-glycan processing enzymes and a major player in the glycoprotein folding quality control, has been described as a soluble heterodimer composed of α and β subunits. Here we present the first characterization of a plant glucosidase II α subunit at the molecular level. Expression of the Arabidopsis α subunit restored...
Article
Full-text available
Glucosidase II, one of the early N-glycan processing enzymes and a major player in the glycoprotein folding quality control, has been described as a soluble heterodimer composed of alpha and beta subunits. Here we present the first characterization of a plant glucosidase II alpha subunit at the molecular level. Expression of the Arabidopsis alpha s...
Article
Full-text available
It is accepted that glycosyltransferase-generated nucleoside diphosphates are converted to monophosphates in the secretory pathway by nucleoside diphosphatases (NDPases) to provide substrates for antiport transport systems by which entrance of nucleotide sugars from the cytosol into the lumen is coupled to exit of nucleoside monophosphates. Working...
Article
Full-text available
Nucleoside diphosphates generated by glycosyltransferases in the fungal, plant, and mammalian cell secretory pathways are converted into monophosphates to relieve inhibition of the transferring enzymes and provide substrates for antiport transport systems by which the entrance of nucleotide sugars from the cytosol into the secretory pathway lumen i...
Article
Full-text available
It has been proposed that in rat and murine tissues glucosidase II (GII) is formed by two subunits, GIIalpha and GIIbeta, respectively, responsible for the catalytic activity and the retention of the enzyme in the endoplasmic reticulum (ER). To test this proposal we disrupted genes (gls2alpha(+) and gls2beta(+)) encoding GIIalpha and GIIbeta homolo...
Article
Full-text available
It has been proposed that in rat and murine tissues glucosidase II (GII) is formed by two subunits, GIIα and GIIβ, respectively, responsible for the catalytic activity and the retention of the enzyme in the endoplasmic reticulum (ER). To test this proposal we disrupted genes (gls2α + andgls2β +) encoding GIIα and GIIβ homologs in Schizosaccharomyce...
Article
Interaction of monoglucosylated oligosaccharides with ER lectins (calnexin and/or calreticulin) facilitates glycoprotein folding but this interaction is not essential for cell viability under normal conditions. We obtained two distinct single Schizosaccharomyces pombe mutants deficient in either one of the two pathways leading to the formation of m...
Article
Full-text available
A key element in the quality control of glycoprotein folding is the UDP-Glc:glycoprotein glucosyltransferase (GT), which in cell-free assays exclusively glucosylates misfolded glycoproteins. In order to test if such a protein conformation is a sufficient condition for in vivo glucosylation of all N-linked oligosaccharides by GT, a Schizosaccharomyc...
Article
Previous work indicated that diacylglycerol (DG) molecules translocate across the cytoplasm of mammalian cells, a process relevant to the signalling role of this lipid as protein kinase C activator. Here we investigated the possible mechanism underlying DG translocation. We examined the interaction between 1,2-di-[1-14C]oleoyl-sn-glycerol and rat l...

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Projects (5)
Project
The goal of the project is to produce a low cost antigen to be use in diagnosis (antibodies detection), therapies (generation of neutralizing antibodies, and prevention (vaccine antigen production)