Vai al contenuto| Home page|

   Ti trovi in: HOME »Programmi, progetti e risultati »I progetti »PRIN - Programmi di ricerca di Rilevante Interesse Nazionale»Programma di ricerca
INIZIO_TESTO_DA_INDICIZZARE

RESEARCH PROGRAM

italiano - inglese
Research Units
Similar research programs:
Scientific and education field classification
International Patent Classification
Geographical classification
Bibliografia
1 Sitia R., Braakman I. (2003). Quality control in the endoplasmic reticulum protein factory.
NATURE. 426: 891-894

2 Fagioli C., Sitia R. (2001). Glycoprotein quality control in the endoplasmic reticulum: Mannose trimming by ER Mannosidase I times the proteasomal degradation of unassembled immunoglobulin subunits. JOURNAL OF BIOLOGICAL
CHEMISTRY. 276:12885-12892

3 Mezghrani A. et Al. , (2001). Manipulation of Oxidative Protein Folding and PDI Redox State in Mammalian Cells. EMBO JOURNAL. 20: 6288-6296

4 Cabibbo A. et Al. (2000). ERO1-L, a human protein that favours disulfide bond formation in the endoplasmic reticulum. JOURNAL OF BIOLOGICAL CHEMISTRY.
275: 4827-4833.

5 Mancini R. et Al. (2000). Degradation of unassembled soluble Ig subunits by cytosolic proteasomes: evidence that retrotranslocation and degradation are couple events. FASEB JOURNAL. 14: 769-778

6 Anelli T. et Al. (2003). Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44. EMBO JOURNAL. 22: 5015-5022

7 Anelli T. et Al. (2002). ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO JOURNAL. 21: 835-844

8 Sarnataro D. et Al. (2004). PrP(C) association with lipid rafts in the early secretory pathway stabilizes its cellular conformation. MOL. BIOL. CELL 15: 4031-4042

9 Campana, V., Sarnataro, D. and Zurzolo, C. (2005). The highways and byways of prion protein trafficking. TRENDS CELL BIOL. 15: 102-111

10 Springer, S., Spang, A., and Schekman, R., (1999). A primer on vesicle budding. CELL 97: 145-148

11 Miller E.A., et al., (2003). Multiple cargo binding sites on the COPII subunit Sec24p ensure capture of diverse membrane proteins into transport vesicles. CELL 114: 497-509

12 Iodice L. et Al. (2001) The carboxyl-terminal valine is required for transport of glycoprotein CD8a from the endoplasmic reticulum to the intermediate compartment. J. BIOL. CHEM. 276: 28920-289226

13 Barr, F.A., N. Nakamura, and G. Warren. (1998). Mapping the interaction between GRASP65 and GM130, components of a protein complex involved in the stacking of Golgi cisternae. EMBO J. 15: 3258-3268

14. Marra F. et Al. (2001). The GM130 and GRASP65 Golgi proteins cycle through and define a subdomain of the intermediate compartment. NAT. CELL. BIOL. 3: 1101-1113

15. Kondylis,V., Spoorendonk, K.M. and Rabouille, C. (2005) dGRASP Localization and Function in the Early Exocytic Pathway in Drosophila S2 Cells. MOL. BIOL. CELL 16: 4061-4072

16. Puthenveedu A. et Al. (2006.) GM130 and GRASP65-dependent lateral cisternal
fusion allows uniform Golgi-enzyme distribution NAT. CELL BIOL. 8: 238-248

17. Sutterlin C. et Al. (2002). Fragmentation and dispersal of the pericentriolar Golgi complex is required for entry into mitosis in mammalian cells CELL 109: 359–369

18 Sonnichsen B. et Al. (1998). A role for giantin in docking COPI vesicles to Golgi membranes J. CELL BIOL. 140: 1013-1021

19 Pelham H.R.B. (1991). Recycling of proteins between the endoplasmic
reticulum and Golgi complex (review). CURR. OPIN. CELL BIOL. 3: 585–591

20 Letourneur F., et Al. (1994). Coatomer is essential for retrieval of dilysines-tagged proteins to the endoplasmic reticulum. CELL 79: 1199–1207.

21 Semenza J.C., et Al. (1990). ERD2, a yeast gene required for the receptor-mediated retrieval of luminal ER proteins from the secretory pathway. CELL 61: 1349–1357
<br />22. Stornaiuolo M. et Al. (2003). KDEL and KKXX retrieval signals appended to the same reporter protein determine different trafficking between endoplasmic reticulum, intermediate compartment, and Golgi complex. MOL. BIOL. CELL 14: 889-902

23 Pedrazzini, E., Villa, A., and Borgese, N. (1996). A mutant cytochrome b5 with a lengthened membrane anchor escapes from the endoplasmic reticulum and reaches the plasma membrane. PROC. NATL. ACAD. SCI. USA 93: 4207-4212

24 Ceppi, P. et Al. (2005). Two tail-anchored protein variants, differing in transmembrane domain length and intracellular sorting, interact differently with lipids. PROC NATL ACAD SCi U S A 102: 16269-74

25 Yamamoto K. et Al. (2003). The KDEL receptor modulates the endoplasmic reticulum stress response through mitogen-activated protein kinase signaling cascade. J. BIOL. CHEM. 278: 34525-34532

26 Hamada H. et Al. (2004). Dilated cardiomyopathy caused by aberrant endoplasmic reticulum quality control in mutant KDEL receptor transgenic mice. MOL. CELL. BIOL. 24: 8007-8017

27 Bard F. et Al. (2003). Src regulates Golgi structure and KDEL receptor-rependent retrograde transport to the endoplasmic reticulum. J. BIOL. CHEM. 278: 46601-46606

28 Higo et Al. (2005). Subtype-specific and ER lumenal environment-dependent regulation of inositol 1,4,5-trisphosphate receptor type 1 by ERp44. CELl 2005 14: 120: 85-98

29 Li, Y., Camacho, P. (2004). Ca2+-dependent redox modulation of SERCA 2b by ERp57. J CELL BIOL. 164: 35-46

30 Sun J. et Al. (2001). Classes of thiols that influence the activity of the skeletal muscle calcium release channel. J. BIOL. CHEM. 276: 15625–15630
Keywords
PROTEIN SYNTHESIS AND FOLDING, MEMBRANE PROTEIN, ENDOPLASMIC RETICULUM, PROTEIN TRANSPORT, INTERMEDIATE COMPARTMENT, GOLGI COMPLEX, LIPID MICRODOMAINS, SIGNALING ORIGINATING FROM THE ENDOPLASMIC RETICULUM

Physiology and pathology of protein folding, trafficking and signaling in the endoplasmic reticulum

Università degli Studi di Napoli "Federico II"
Abstract
The endoplasmic reticulum (ER) is a hallmark of eukaryotic cell biology, and is responsible for numerous vital interconnected processes linked to general cell behaviors, such as response to stress and apoptosis. The goal of this project is to contribute to the definition of molecular mechanisms underlying central functions of the ER – protein folding and selection of cargo proteins for export, signaling to and from the ER -, functions that not only have a primary role in the homeostasis of the ER, the Golgi complex, and the Intermediate Compartment between ER and Golgi (IC), but are also involved in human pathologies. Moreover, in industry, the low production of human proteins of clinical utility is often caused by their inefficient transport in heterologous systems. Therefore, a better understanding of these mechanisms may have important implications for medicine and biotechnology.

Here we summarize the 4 principal lines of the project.

1. Protein folding in the ER
A central function of the ER is to assist the folding of newly synthesized proteins, hindering the inappropriate transport of malfolded proteins. In this project, we will characterize the functions of a recently identified protein involved in oxidative folding, ERp44: we will study its role in the folding and transport of IgM, of prion protein and of coagulation factors V and VIII, its localization in the ER/IC system, and its interaction with protein partners identified >>>

Principal Investigator
Stefano Bonatti Università degli Studi di NAPOLI "Federico II"
Research Objectives
The goal of this project is to contribute to the definiton of molecular mechanisms underlying fundamental functions of the Endoplasmic Reticulum (ER) and of the functional association of the ER with the Intermediate Compartment between the ER and the Golgi (IC) and the Golgi itself:

1. Folding, quality control (QC) and redox systems of the ER
2. Routes for the selective transport of proteins from and to the ER
3. Possible role of lipid microdomains in the folding and sorting of proteins in the ER
4. Signaling pathways originating in the ER

Although for explanatory purposes we have listed these functions separately, they are in fact tightly interconnected, so that they must be studied in an integrated fashion. This is the reason for coordinating 4 research groups in the present research proposal. The 4 groups have been working for many years on the ER, and have played a recognized role in the development and the promotion of cell molecular biology in Italy. Each group has developed a distinct expertise, and a specific set of experimental systems and reagents. It is hoped that a large number of novel results will be produced through direct collaboration between the groups, exchange of information and sharing of reagents and methods well before their publication. To favor such collaboration, the participants will meet twice a year: in the spring within the annual ABCD satellite meeting “Membrane Traffic and Organelle >>>

Timescale
24 months
National and international background
The Endoplasmic Reticulum (ER) is a hallmark of eukaryotic cell biology, being responsible for many processes of fundamental importance, such as 1) Biogenesis, folding, selection and transport of proteins trafficking to the distal compartments of the exocytic pathway; 2) Synthesis and regulation of membrane lipids; 3) Cellular responses to stress and activation of apoptosis; 4) Intracellular calcium homeostasis. Recent research has revealed that all these functions are tightly interlinked so that the understanding of each single function must be integrated with that of the others. Here we discuss some aspects of ER biology that have been uncovered by recent research which underline the strong connection between the many roles of this organelle.

A. Protein folding in the ER.
Efficient cell function requires that proteins that are secreted or exposed on the cell surface have correct spatial conformations. Cells must therefore block the transport of potentially toxic misfolded proteins. Thus, an important function of the ER is to assist the folding of newly-synthesized proteins, such that only properly folded proteins are exported towards the surface. Conversely, misfolded proteins are retained in the ER (quality control –QC), retrotaslocated to the cytosol and degraded by the proteasome (ER Associated Degradation – ERAD). One of the most important events during protein maturation is their oxidative folding. The ER lumen contains numerous enzymes involved >>>