Chiara Zurzolo
Chiara Zurzolo
affiliation: Università di Napoli Federico II
research area(s): Cell Biology, Neuroscience
Course: Genetics and Molecular Medicine
University/Istitution: Università di Napoli Federico II
1980-1984: Research training as MD Student at the Institute of "Patologia Generale" Naples University Medical School. Subject of study: Morphological and functional characterization of thyroid follicles in primary culture

7/82-9/82: Guest worker at the laboratory of Dr. H. Edelhoch CEB/NIADDKD, NIH Bethesda, USA. Subject of study: Role of coated vesciles in thyroglobulin transport

7/83-10/83: Guest worker at the laboratory of Dr. H. Edelhoch CEB/NIADDKD, NIH Bethesda, USA. Subject of study: Biosynthesis and assembly of clathrin chains in rat liver

1/85-12/86: AIRC fellow in the laboratory of Dr.Lucio Nitsch, Naples University Medical School
Subject of study: Role of extracellular matrix in thyroid differentiation

9/86-2/91: Ph.D student with Prof.. Lucio Nitsch at Naples University. Subject of study: Mechanism of development of cell polarity in thyroid epithelial cells

4/90-12/94: Postdoctoral Fellow in the laboratory of Dr. Enrique Rodriguez-Boulan, Department of Cell Biology and Anatomy, Cornell University Medical College, New York, NY
Subject of study: Mechanism of protein sorting in polarized rat thyroid epithelial cells

1994-1999: Assistant Professor of Cell Biology at Naples University Medical School-Department of Cellular and Molecular Biology and Pathology. Subject of study: Sorting signals and molecular mechanisms of apical and basolateral protein sorting in thyroid epithelial cells

1999 to date: Associate Professor of Cell Biology at Naples University Medical School-Department of Cellular and Molecular Biology and Pathology. Subject of study: Molecular mechanism of protein trafficking in epithelial cells and Intracellular trafficking and prion conversion.
The lab focuses on two major research projects:
1) Understanding the mechanism of GPI-anchored protein sorting to the plasma membrane of polarized epithelial cells
2) Study of the intracellular trafficking of the prion protein, the site of conversion and the mechanisms of intercellular spreading

They utilize both classical biochemical and molecular biology approaches and the state-of-the-art techniques of live cell imaging.
For the GPI-APs sorting project, they pioneered conditions to show direct delivery of proteins to the apical membrane in live polarized cells grown on filters (Paladino et al 2006), and have set up FRAP and FLIM at the PM and golgi in order to analyse the membrane environment and proximity of apical and basolateral GPI-APs (Lebreton et al 2008). They have shown that different GPI-attachment signal mediate differential sorting and association to lipid domains of GPI-APs (Paladino et al 2008). She has proposed that protein oligomerization is essential for apical sorting (Paladino et al, 2004) and is dependent on both the ectodomain and the lipid anchor/and or environment (Catino et al. 2008, Paladino et al 2007, Lebreton et al 2008). They are currently analyzing at super resolution level (by PALM and STORM Microscopy) the organization of different GPI-APs at the plasma membrane and its relation with both the protein sorting and function.
For the prion project they have analyzed the exocytic/endocytic trafficking of PrPC and of some mutants responsible for the hereditary diseases (Campana et al, 2005, Campana et al, 2007). They proposed that raft environment might stabilize the proper folding of PrPC and may protect PrP mutants from conversion (Campana et al, 2005, Campana et al, 2006, Sarnataro et al, 2006). Another important discovery is that that prion conversion occurs in the recycling compartment (Marijanovic et al 2009). This will open the door to more targeted approaches to identify the factors involved in the disease and to develop better therapeutic strategies. Last but not least, Dr Zurzolo"s lab discovered that Tunnelling Nanotubes (thin membranous connection between distant cells) are responsible of the spreading of infectious prions (Gousset et al, 2009). Based on these data she proposes that through the establishments of TNTs, peripheral dendridic cells can spread infection to neurons of the PNS and then by retrograde transport to the CNS. They are currently studying the mechanism of TNTs formation and their involvement in other neurodegenerative diseases.
1. Paladino S, Sarnataro D, Pillich R, Tivodar S, Nitsch L & Zurzolo C (2004) Protein oligomerization modulates raft partitioning and apical sorting of GPI-anchored proteins. The Journal of Cell Biology, 167(4):699-709

2. Sarnataro D, Campana V, Paladino S, Stornaiuolo M, Nitsch L & Zurzolo C (2004) PrP(C) association with lipid rafts in the early secretory pathway stabilizes its cellular conformation. Molecular Biology of the Cell, 15(9):4031-4042

3. Paladino S, Pocard T, Catino MA & Zurzolo C (2006) GPI-anchored proteins are directly targeted to the apical surface in fully polarized MDCK cells. The Journal of Cell Biology, 172(7):1023-1034

4. Campana V, Sarnataro D, Fasano C, Casanova P, Paladino S & Zurzolo C (2006) Detergent-resistant membrane domains but not the proteasome are involved in the misfolding of a PrP mutant retained in the endoplasmic reticulum. Journal of Cell Science, 119(433-442)

5. Pocard T, Le Bivic A, Galli T & Zurzolo C (2007) Distinct v-SNAREs regulate direct and indirect apical delivery in polarized epithelial cells. Journal of Cell Science, 120 (Pt 18):3309-20

6. Paladino S, Lebreton S, Tivodar S, Campana V, Tempre R & Zurzolo C (2008) Different GPI-attachment signals affect the oligomerisation of GPI-anchored proteins and their apical sorting. Journal of Cell Science, 121(Pt 24):4001-4007

7. Schiff E, Campana V, Tivodar S, Lebreton S, Gousset K & Zurzolo C (2008) Coexpression of wild-type and mutant PrPs alters their cellular localization and partitioning into detergent resistant membranes. Traffic, 9(7):1101-1115(15)

8. Lebreton S, Paladino S & Zurzolo C (2008) Selective roles for cholesterol and actin in compartmentalization of different proteins in the Golgi and plasma membrane of polarized cells. The Journal of Biological Chemistry , 283(43)29545-53

9. Gousset K, Schiff E, Langevin C, Marijanovic Z, Caputo A, Browman D, Chenouard N, de Chaumont F, Martino A, Enninga J, Olivo-Marin JC, Männel D & Zurzolo C (2009) Prions hijack tunnelling nanotubes for intercellular spread. Nature Cell Biology, 11(3):328-36

10. Marijanovic Z, Caputo A, Campana V & Zurzolo C (2009) Identification of the intracellular site of prion conversion. PLoS Pathogens, 5(5): e1000426
Project Title:
Analysis of the mechanism of GPI-APs sorting in living epithelial cells.

Project Title:
Analysis of the role of Tunnelling Nanotubes in the progression of Hungtinton and Parkinson diseases.