A5014520599- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- Prenatal Screening and Diagnostics
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Mitochondrial Function and Pathology
- Down syndrome and intellectual disability research
- RNA modifications and cancer
- Erythrocyte Function and Pathophysiology
- Animal Genetics and Reproduction
- RNA regulation and disease
- Thyroid Disorders and Treatments
- Wnt/β-catenin signaling in development and cancer
- RNA Research and Splicing
- S100 Proteins and Annexins
- Genomics and Rare Diseases
- Hippo pathway signaling and YAP/TAZ
- Prion Diseases and Protein Misfolding
- Protease and Inhibitor Mechanisms
- Viral gastroenteritis research and epidemiology
- Cancer-related gene regulation
- Cellular Mechanics and Interactions
- Glycosylation and Glycoproteins Research
- Chromosomal and Genetic Variations
- TGF-β signaling in diseases
University of Naples Federico II
2014-2023
Institute for Experimental Endocrinology and Oncology
2004-2023
National Research Council
2002-2023
Federico II University Hospital
2010-2020
Ceinge Biotecnologie Avanzate (Italy)
2012
Universität Hamburg
2012
University Medical Center Hamburg-Eppendorf
2012
National Center on Birth Defects and Developmental Disabilities
2009-2012
Biogem
2004-2007
Cornell University
1992-1998
An essential but insufficient step for apical sorting of glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) in epithelial cells is their association with detergent-resistant microdomains (DRMs) or rafts. In this paper, we show that MDCK both and basolateral GPI-APs associate DRMs during biosynthesis. However, only not are able to oligomerize into high molecular weight complexes. Protein oligomerization begins the medial Golgi, concomitantly DRM association, dependent on...
In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as model for investigating the molecular mechanisms terminal that are currently poorly understood. We characterized level genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple (72%), ring chromosomes (14%), and unbalanced translocations (7%). also discovered interstitial between 17–74 kb 9% patients. Haploinsufficiency SHANK3 gene,...
Alterations in mitochondrial activity and morphology have been demonstrated human cells tissues from individuals with Down syndrome (DS), as well DS mouse models. An impaired of the transcriptional coactivator PGC-1α/PPARGC1A due to overexpression chromosome 21 genes, such NRIP1/RIP140, has emerged an underlying cause dysfunction DS. We tested hypothesis that activation PGC-1α pathway might indeed reverse this dysfunction. To end, we investigated effects metformin, a PGC-1α-activating drug,...
Glycosylphosphatidylinositol (GPI) acts as an apical targeting signal in MDCK cells and other kidney intestinal cell lines. In striking contrast with these model polarized lines, we show here that Fischer rat thyroid (FRT) epithelial do not display a preferential distribution of GPI-anchored proteins. Six out nine detectable endogenous proteins were localized on the basolateral surface, whereas two others one was polarized. Transfection several GPI proteins, previously shown to be apically...
Abstract Background The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21) genes. However, the expression profile Hsa21 genes in trisomic human subjects as well their effects on located different chromosomes are largely unknown. Using oligonucleotide microarrays we compared gene profiles hearts fetuses with and without trisomy. Results Approximately half 15,000 examined (87 168 Hsa21) were expressed heart at 18–22 weeks gestation. was globally upregulated...
Most epithelial cells sort glycosylphosphatidylinositol (GPI)-anchored proteins to the apical surface. The “raft” hypothesis, based on data mainly obtained in prototype cell line MDCK, postulates that sorting depends incorporation of into cholesterol/glycosphingolipid (GSL) rafts, rich cholesterol binding protein caveolin/VIP21, Golgi apparatus. Fischer rat thyroid (FRT) constitute an ideal model test this since they missort both endogenous and transfected GPI- anchored basolateral plasma...
Pax genes encode for transcription factors essential tissue development in many species. Pax8, the only member of family expressed thyroid tissue, is involved morphogenesis gland and transcriptional regulation thyroid-specific genes. TTF-1, a homeodomain-containing factor, also has been demonstrated to play role gene expression. Despite presence Pax8 TTF-1 few other tissues, simultaneous expression two occurs thyroid, supporting idea that might cooperate influence In this report, we describe...
The pathological conversion of cellular prion protein (PrP C ) into the scrapie Sc isoform appears to have a central role in pathogenesis transmissible spongiform encephalopathies. However, identity intracellular compartment where this occurs is unknown. Several lines evidence indicate that detergent-resistant membrane domains (DRMs or rafts) could be involved process. We characterized association PrP rafts during its biosynthesis. found associates with already as an immature precursor...
Trisomy of chromosome 21 is associated to congenital heart defects in ∼50% affected newborns. Transcriptome analysis hearts from trisomic human foeti demonstrated that genes involved mitochondrial function are globally downregulated with respect controls, suggesting an impairment function. We investigated here the properties mitochondria fibroblasts and without cardiac defects. Together upregulation Hsa21 downregulation nuclear encoded genes, abnormal cristae morphology was observed samples....
In contrast to Madin–Darby canine kidney cells, Fischer rat thyroid cells deliver the majority of endogenous glycosylphosphatidyl inositol (GPI)–anchored proteins basolateral surface. However, we report here that GPI Placental Alkaline Phosphatase (PLAP) and Neurotrophin Receptor–Placental (NTR-PLAP) are apically localized in transfected cells. agreement with “raft hypothesis,” which postulates incorporation into glycosphingolipids cholesterol-enriched rafts, found both these were insoluble...
Separated thyroid follicles can be maintained in suspension culture Coon's modified F-12 medium 0.5% calf serum. If the serum concentration is raised to 5%, undergo inversion 3-5 d. During process of inversion, epithelial cells observed intermediate stages polarity reversal. The earliest ultrastructural changes recognized are surface which tight junctions and microvilli appear at lateral margins cell near medium. Later, distribution intracellular organelles occur. Golgi apparatus shifts...
Abstract Recently, a new form of autosomal recessive early-onset parkinsonism (PARK20), due to mutations in the gene encoding phosphoinositide phosphatase, Synaptojanin 1 (Synj1), has been reported. Several genes responsible for hereditary forms Parkinson’s disease are implicated distinct steps endolysosomal pathway. However, nature and degree endocytic membrane trafficking impairment remains elusive. Here, we show that depletion Synj1 causes drastic alterations early endosomes, which become...
PARK20, an early onset autosomal recessive parkinsonism is due to mutations in the phosphatidylinositol-phosphatase Synaptojanin 1 (Synj1). We have recently shown that endosomal compartments are profoundly altered PARK20 fibroblasts as well trafficking. Here, we report also display a drastic alteration of architecture and function secretory compartments. Our results show exit machinery from Endoplasmic Reticulum (ER) ER-to-Golgi trafficking markedly compromised patient cells. As consequence,...
PrP C is a glycosylphosphatidylinositol‐anchored protein expressed in neurons as well the cells of several peripheral tissues. Although normal function remains unknown, conformational isoform called Sc (scrapie) has been proposed to be infectious agent transmissible spongiform encephalopathies animals and humans. Where how conversion occurs not yet known. Therefore, dissecting intracellular trafficking wild‐type prion protein, scrapie isoform, can major relevance pathogenesis diseases. In...
Dedifferentiated chick embryo chondrocytes (Castagnola, P., G. Moro, F. Descalzi-Cancedda, and R. Cancedda, 1986, J. Cell Biol., 102:2310-2317), when transferred to suspension culture on agarose-coated dishes in the presence of ascorbic acid, aggregate remain clustered. With time culture, clusters grow size adhere each other, forming structures that may be several millimeters dimension. These after 7 d have histologic appearance mature hypertrophic cartilage partially surrounded by a layer...
We have been investigating the extent to which separated thyroid follicles in suspension culture, free of endothelium and fibroblasts, properties vivo. To test whether thyrotropin (TSH) can cause epithelial cells undergo mitosis, preparations suspended Coon's modified F-12 medium with 0.5% calf serum were incubated 10 milliunits impure or pure TSH per ml. Three results obtained: (i) stimulated incorporation [3H]thymidine into cell nuclei; (ii) mitotic figures induced they had same...
We have prepared thyroid follicles in suspension culture to use as a model system vitro for investigation of some properties the gland. The were free endothelial cells, fibroblasts, and other nonepithelial cells. They by collagenase treatment minced rat glands followed differential filtration through nylon meshes. Small clusters principal epithelial cells separated from large fragments single cultured dilute Coon's modified F-12 medium dishes coated with agarose avoid having attach dishes....
Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), class small non-coding RNAs regulating gene expression at post-transcriptional level. To explore functional role miRNAs in thyroid gland function, we generated thyrocyte-specific conditional knockout mouse. Here show that development and early differentiation are not affected by absence Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight shortened life span....
We compared the surface envelope glycoprotein distribution and budding polarity of four RNA viruses in Fischer rat thyroid (FRT) cells CaCo-2 derived from a human colon carcinoma. Whereas both FRT sort similarly influenza hemagglutinin vesicular stomatitis virus (VSV) G protein, respectively, to apical basolateral membrane domains, they differ their handling two togaviruses, Sindbis Semliki Forest (SFV). By conventional EM SFV were shown bud apically basolaterally cells. Consistent with this...