A5027971423- Advanced Breast Cancer Therapies
- Estrogen and related hormone effects
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Breast Cancer Treatment Studies
- melanin and skin pigmentation
- Mitochondrial Function and Pathology
- Retinal Development and Disorders
- Retinoids in leukemia and cellular processes
- Osteoarthritis Treatment and Mechanisms
- HER2/EGFR in Cancer Research
- Biochemical Analysis and Sensing Techniques
- ATP Synthase and ATPases Research
- Autophagy in Disease and Therapy
- Adenosine and Purinergic Signaling
- Advanced Electron Microscopy Techniques and Applications
- Cancer-related Molecular Pathways
- COVID-19 Clinical Research Studies
- Lipid Membrane Structure and Behavior
- HIV Research and Treatment
- Neuroscience and Neuropharmacology Research
- Immune Cell Function and Interaction
- Receptor Mechanisms and Signaling
- Radiomics and Machine Learning in Medical Imaging
- Endoplasmic Reticulum Stress and Disease
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2025
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2016-2025
Vita-Salute San Raffaele University
2016-2025
IRCCS Ospedale San Raffaele
1994-2024
University of Genoa
2010-2022
San Raffaele University of Rome
2010-2022
IFOM
2004-2012
Molecular Oncology (United States)
2008
University of Milan
2005
European Institute of Oncology
2004-2005
Plasma membrane receptors can be endocytosed through clathrin-dependent and clathrin-independent pathways. Here, we show that the epidermal growth factor (EGF) receptor (EGFR), when stimulated with low doses of EGF, is internalized almost exclusively clathrin pathway, it not ubiquitinated. At higher concentrations ligand, however, a substantial fraction clathrin-independent, lipid raft-dependent route, as becomes An ubiquitination-impaired EGFR mutant was whereas an EGFR/ubiquitin chimera,...
G-protein-coupled receptors (GPCRs) are generally thought to signal second messengers like cyclic AMP (cAMP) from the cell surface and become internalized upon repeated or prolonged stimulation. Once internalized, they supposed stop signaling but may trigger nonclassical signals such as mitogen-activated protein kinase (MAPK) activation. Here, we show that a GPCR continues stimulate cAMP production in sustained manner after internalization. We generated transgenic mice with ubiquitous...
Receptor endocytosis is a fundamental step in controlling the magnitude, duration, and nature of cell signaling events. Confluent endothelial cells are contact inhibited their growth respond poorly to proliferative signals vascular factor (VEGF). In previous study, we found that association cadherin (VEC) with VEGF receptor (VEGFR) type 2 contributes density-dependent inhibition (Lampugnani, G.M., A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, Orsenigo, Cattelino, R. Kemler,...
Most lysosomal storage disorders (LSDs) are caused by deficiencies of hydrolases. While LSDs were among the first inherited diseases for which underlying biochemical defects identified, mechanisms from enzyme deficiency to cell death poorly understood. Here we show that impairs autophagic delivery bulk cytosolic contents lysosomes. By studying mouse models two associated with severe neurodegeneration, multiple sulfatase (MSD) and mucopolysaccharidosis type IIIA (MPSIIIA), observed an...
The promyelocytic leukemia (PML) tumor suppressor is a pleiotropic modulator of apoptosis. However, the molecular basis for such diverse proapoptotic role currently unknown. We show that extranuclear Pml was specifically enriched at endoplasmic reticulum (ER) and mitochondria-associated membranes, signaling domains involved in ER-to-mitochondria calcium ion (Ca(2+)) transport induction found complexes large size with inositol 1,4,5-trisphosphate receptor (IP(3)R), protein kinase Akt,...
CD8+ T cells are master effectors of antitumor immunity, and their presence at tumor sites correlates with favorable outcomes. However, metabolic constraints imposed by the microenvironment (TME) can dampen ability to control progression. We describe lipid accumulation in TME areas pancreatic ductal adenocarcinoma (PDA) populated infiltrating both murine human tumors. In this lipid-rich but otherwise nutrient-poor TME, access using metabolism becomes particularly valuable for sustaining cell...
This Viewpoint discusses the Trustworthy and Responsible AI Network Europe (TRAIN-Europe) consortium, an effort of medical experts to oversee, develop, share ethical practices through collaboration technological solutions designed implement responsible practices.
Integrin-mediated cell adhesion cooperates with growth factor receptors in the control of proliferation, survival, and migration. One mechanism to explain these synergistic effects is ability integrins induce phosphorylation receptors, for instance epidermal (EGF) receptor. Here we define some aspects molecular mechanisms regulating integrin-dependent EGF receptor phosphorylation. We show that early phases associate on membrane a macromolecular complex including adaptor protein p130Cas c-Src...
Numb is a protein that in Drosophila determines cell fate as result of its asymmetric partitioning at mitosis. The function has been linked to ability bind and biologically antagonize Notch, membrane receptor also specifies fate. biochemical mechanisms underlying the action Numb, however, are still largely unknown. wide pattern expression suggests general cellular homeostasis could be additional to, or part of, determination. Such endocytosis, suggested by interaction with Eps15, component...
P66Shc regulates life span in mammals and is a critical component of the apoptotic response to oxidative stress. It functions as downstream target tumor suppressor p53 indispensable for ability stress-activated induce apoptosis. The molecular mechanisms underlying apoptogenic effect p66Shc are unknown. Here we report following three findings. (i) apoptosome can be properly activated vitro absence only if purified cytochrome c supplied. (ii) Cytochrome release after signals impaired p66Shc....
The role of dense core secretory vesicles in the control cytosolic-free Ca(2+) concentrations ([Ca(2+)](c)) neuronal and neuroendocrine cells is enigmatic. By constructing a vesicle-associated membrane protein 2-synaptobrevin.aequorin chimera, we show that clonal pancreatic islet beta-cells: (a) increases [Ca(2+)](c) cause prompt increase intravesicular-free concentration ([Ca(2+)]SV), which mediated by P-type Ca(2+)-ATPase distinct from sarco(endo) plasmic reticulum Ca(2+)-ATPase, but may...
Abstract Purpose: Antigenic overlap among circulating endothelial cells (CEC) and progenitors (CEP), platelets, other blood led to the need develop a reliable standardized method for CEC CEP quantification. These are emerging as promising preclinical/clinical tools define optimal biological doses of antiangiogenic therapies help stratify patients in clinical trials. Experimental Design: We report experimental validation novel flow cytometry that precisely dissects CEC/CEP from platelets cell...
Evidence indicates that endosomal entry promotes signaling by the Notch receptor, but mechanisms involved are not clear. In a search for factors regulate activation in endosomes, we isolated mutants Drosophila genes encode subunits of vacuolar ATPase (V-ATPase) proton pump. Cells lacking V-ATPase function display impaired acidification compartment and correlated failure to degrade endocytic cargoes. mutant cells internalize accumulate it lysosome, surprisingly also show substantial loss both...
Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, with grim prognosis a half of patients. Exosomes are nanometer-sized membrane vesicles derived from multivesicular bodies (MVBs) endocytic pathway and released by normal neoplastic cells. Tumor-derived exosomes have been shown different model systems to carry molecules that promote cancer growth dissemination. In this respect, we here performed first characterization proteomic analysis isolated human NB cell lines...
The precise molecular mechanisms that coordinate apoptosis and autophagy in cancer remain to be determined. Here, we provide evidence the tumor suppressor promyelocytic leukemia protein (PML) controls autophagosome formation at mitochondria-associated membranes (MAMs) and, thus, induction. Our vitro vivo results demonstrate how PML functions as a repressor of autophagy. loss promotes development, providing growth advantage cells use cell survival strategy during stress conditions. These...
ER-PM contacts in nonclathrin endocytosis The epidermal growth factor receptor (EGFR) is internalized through both clathrin-mediated and (NCE). two pathways act concert to sustain EGFR signaling or its long-term attenuation. mechanistic underpinnings of EGFR-NCE are unclear. Caldieri et al. used a variety cell molecular biology approaches identify nine regulators (see the Perspective by Tan Anderson). They also identified an additional cargo pathway (CD147). One was endoplasmic reticulum...
Live-cell microscopy has highlighted that transcription factors bind transiently to chromatin but it is not clear if the duration of these binding interactions can be modulated in response an activation stimulus, and such modulation controlled by post-translational modifications factor. We address this question for tumor suppressor p53 combining live-cell single-molecule single cell situ measurements we show p53-binding kinetics are following genotoxic stress. The residence times on requires...
In late 2019, the betacoronavirus SARS-CoV-2 was identified as viral agent responsible for coronavirus disease 2019 (COVID-19) pandemic. Coronaviruses Spike proteins are their ability to interact with host membrane receptors and different have been interactors, among which Angiotensin-converting enzyme 2 (ACE2), Basigin2/EMMPRIN/CD147 (CD147). CD147 plays an important role in human immunodeficiency virus type 1, hepatitis C virus, B Kaposi’s sarcoma-associated herpesvirus, severe acute...
Adaptor protein 2 (AP2) is a major constituent of clathrin-coated pits (CCPs). Whether it essential for all forms clathrin-mediated endocytosis (CME) in mammalian cells an open issue. Here, we demonstrate, by live TIRF microscopy, the existence subclass relatively short-lived CCPs lacking AP2 under physiological, unperturbed conditions. This retained AP2-knockout and able to support internalization epidermal growth factor receptor (EGFR) but not transferrin (TfR). The AP2-independent...
Leber's hereditary optic neuropathy (LHON), a disease associated with mitochondrial DNA mutation, is characterized by blindness due to degeneration of retinal ganglion cells (RGCs) and their axons, which form the nerve.We show that sustained pathological autophagy compartment-specific mitophagy activity affects LHON patient-derived cybrids, as well induced pluripotent-stem-cell-derived neurons.This variably counterbalanced compensatory mitobiogenesis.The aberrant quality control disrupts...
Nuclear factors rapidly scan the genome for their targets, but role of nuclear organization in such search is uncharted. Here we analyzed how multiple explore chromatin, combining live-cell single-molecule tracking with multifocal structured illumination DNA density. We find that displaying higher bound fractions sample DNA-dense regions more exhaustively. Focusing on tumor-suppressor p53, demonstrate it searches targets by alternating between rapid diffusion interchromatin compartment and...