- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Ion channel regulation and function
- Genetics and Neurodevelopmental Disorders
- Lipid Membrane Structure and Behavior
- RNA Interference and Gene Delivery
- Amyotrophic Lateral Sclerosis Research
- Cell Adhesion Molecules Research
- Advanced Fluorescence Microscopy Techniques
- Photoreceptor and optogenetics research
- Autism Spectrum Disorder Research
- Neurogenetic and Muscular Disorders Research
- Autophagy in Disease and Therapy
- Advanced Electron Microscopy Techniques and Applications
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Neuroendocrine regulation and behavior
- Nanoparticle-Based Drug Delivery
- Extracellular vesicles in disease
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Caveolin-1 and cellular processes
- Retinal Development and Disorders
- Cellular Mechanics and Interactions
- Sperm and Testicular Function
University of Milan
2014-2024
Neuroscience Institute
2003-2016
National Research Council
2003-2016
Centre Hospitalier Universitaire de Tivoli
2016
Fondazione Filarete
2011-2015
Ospedale San Filippo Neri
2009
University of Parma
2009
University of Verona
2009
Ospedale Maggiore
2009
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
2009
Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse brown adipocytes and 3T3-L1, U937, HeLa cells. This effect of nitric dependent on guanosine 3′,5′-monophosphate (cGMP) mediated by the induction peroxisome proliferator–activated receptor γ coactivator 1α, a master regulator biogenesis. Moreover, induced exposure cold markedly reduced adipose tissue endothelial synthase null-mutant (eNOS –/– ) mice, which had metabolic rate accelerated weight gain compared...
We recently found that long-term exposure to nitric oxide (NO) triggers mitochondrial biogenesis in mammalian cells and tissues by activation of guanylate cyclase generation cGMP. Here, we report the NO/cGMP-dependent is associated with enhanced coupled respiration content ATP U937, L6, PC12 cells. The observed increase depended entirely on oxidative phosphorylation, because formation glycolysis was unchanged. Brain, kidney, liver, heart, gastrocnemius muscle from endothelial NO synthase...
The endoplasmic reticulum (ER) can transform from a network of branching tubules into stacked membrane arrays (termed organized smooth ER [OSER]) in response to elevated levels specific resident proteins, such as cytochrome b(5). Here, we have tagged OSER-inducing proteins with green fluorescent protein (GFP) study OSER biogenesis and dynamics living cells. Overexpression these induced formation karmellae, whorls, crystalloid structures. Photobleaching experiments revealed that were highly...
Microvesicles (MVs) have been indicated as important mediators of intercellular communication and are emerging new biomarkers tissue damage. Our previous data indicate that reactive microglia/macrophages release MVs in vitro. The aim the study was to evaluate whether released by vivo their number varies brain inflammatory conditions, such multiple sclerosis (MS).Electron fluorescence microscopy flow cytometry were used detect myeloid cerebrospinal fluid (CSF) healthy controls, MS patients,...
Several fluorescent proteins (FPs) are prone to forming low-affinity oligomers. This undesirable tendency is exacerbated when FPs confined membranes or fused naturally oligomeric proteins. Oligomerization of limits their suitability for creating fusions with interest. Unfortunately, no standardized method evaluates the biologically relevant state FPs. Here, we describe a quantitative visual assay assessing whether sufficiently monomeric under physiologic conditions. Membrane-associated...
Cholesterol and sphingolipids are abundant in neuronal membranes, where they help the organisation of membrane microdomains involved major roles such as axonal dendritic growth, synapse spine stability. The aim this study was to analyse their presynaptic physiology. We first confirmed presence proteins exocytic machinery (SNARES Ca(v)2.1 channels) lipid cultured neurons, then incubated neurons with fumonisin B (an inhibitor sphingolipid synthesis), or mevastatin zaragozic acid (two compounds...
Lipid microdomains can selectively include or exclude proteins and may be important in a variety of functions such as protein sorting, cell signaling, synaptic transmission. The present study demonstrates that two different voltage-gated calcium channels, which both interact with soluble N-ethyl-maleimide-sensitive fusion attachment receptor (SNARE) but have distinct subcellular distributions roles transmission, are differently distributed lipid microdomains; presynaptic P/Q (Cav2.1) not Lc...
The SNARE-dependent exocytosis of glutamate-containing vesicles in astrocytes is increasingly viewed as an important signal at the basis astrocyte-to-neurone communication system brain. Here we provide further insights into molecular features and dynamics cultured astrocytes. We found that immunoisolated synaptobrevin2 are clear quite heterogenous size contain vesicular glutamate transporter v-Glut-2. Moreover, they immunopositive for synaptotagmin IV, AMPA receptor subunits GluR2,3 and, to...
VAPB (vesicle-associated membrane protein-associated protein B) is an endoplasmic reticulum (ER)-resident tail-anchored adaptor involved in lipid transport. A dominantly inherited mutant, P56S-VAPB, causes a familial form of amyotrophic lateral sclerosis (ALS) and forms poorly characterized inclusion bodies cultured cells. To provide cell biological basis for the understanding mutant pathogenicity, we investigated its biogenesis inclusions that it generates. Translocation assays cell-free...
The length and hydrophobicity of the transmembrane domain (TMD) play an important role in sorting membrane proteins within secretory pathway; however, relative contributions protein–protein protein–lipid interactions to this phenomenon are currently not understood. To investigate mechanism TMD-dependent sorting, we used following two C tail–anchored fluorescent (FPs), which differ only TMD length: FP-17, is anchored endoplasmic reticulum (ER) by 17 uncharged residues, FP-22, driven plasma...
During the initial stage of neuromuscular junction (NMJ) formation, nerve-derived agrin cooperates with muscle-autonomous mechanisms in organization and stabilization a plaque-like postsynaptic specialization at site nerve-muscle contact. Subsequent NMJ maturation to characteristic pretzel-like appearance requires extensive structural reorganization. We found that progress plaque-to-pretzel is regulated by agrin. Excessive cleavage via transgenic overexpression an agrin-cleaving protease,...
ATP is the main transmitter stored and released from astrocytes under physiological pathological conditions. Morphological functional evidence suggest that besides secretory granules, lysosomes release ATP. However, molecular mechanisms involved in astrocytic lysosome fusion remain still unknown.In present study, we identify tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP, also called VAMP7) as vesicular SNARE which mediates exocytosis, contributing to of both...
Myosin IXa (Myo9a) is a motor protein that highly expressed in the brain. However, role of Myo9a neurons remains unknown. Here, we investigated function hippocampal synapses. In rat neurons, localizes to postsynaptic density (PSD) and binds alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) GluA2 subunit. Myo9a+/- mice displayed thicker PSD increased levels PSD95 surface AMPAR expression. Furthermore, synaptic transmission, long-term potentiation (LTP) cognitive...
Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated pathogenesis neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous involved control protein translation. Here, we show that eEF2K activity negatively regulates GABAergic transmission. Indeed, loss increases by upregulating presynaptic Synapsin 2b α5-containing GABAA receptors thus interferes with excitation/inhibition balance....
Abstract Long-term memory formation (LTM) is a process accompanied by energy-demanding structural changes at synapses and increased spine density. Concomitant increases in both volume postsynaptic density (PSD) surface area have been suggested but never quantified vivo clear-cut experimental evidence. Using novel object recognition mice as learning task followed 3D electron microscopy analysis, we demonstrate that LTM induced all aforementioned synaptic changes, together with an increase the...
The present study demonstrates, by in vitro and vivo analyses, the novel concept that signal transmission between sympathetic neurons heart, underlying physiological regulation of cardiac function, operates a quasi-synaptic fashion. This is result direct coupling neurotransmitter releasing sites effector cardiomyocyte membranes.Cardiac (SNs) finely tune rate strength heart contractions to match blood demand, both at rest during acute stress, through release noradrenaline (NE). Junctional...
Abstract Mature sperm cells have the spontaneous capacity to take up exogenous DNA. Such DNA specifically interacts with subacrosomal segment of head corresponding nuclear area. Part sperm‐bound foreign is further internalized into nuclei. Using end‐labelled plasmid we found that 15–22% total bound associated nuclei as determined on isolated On basis autoradiographic analysis, permeability seems be a wide phenomenon involving majority In fact, DNA, incubated for different lengths time, in...
Granins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter debate. Work cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A B (CgA CgB), involved granulogenesis protein sorting. Here we report generation characterization mice lacking (CgB-ko), which were viable fertile. Unlike tissues, pancreatic islets these animals lacked compensatory changes other granins therefore analyzed...