Ginetta Collo

Publications (29) View all

• Article: Pre-synaptic dopamine D(3) receptor mediates cocaine-induced structural plasticity in mesencephalic dopaminergic neurons via ERK and Akt pathways.

  Ginetta Collo, Federica Bono, Laura Cavalleri, Laura Plebani, Emilio Merlo Pich, Mark J Millan, Pier Franco Spano, Cristina Missale
  [show abstract] [hide abstract]
  ABSTRACT: Exposure to psychostimulants results in neuroadaptive changes of the mesencephalic dopaminergic system including morphological reorganization of dopaminergic neurons. Increased dendrite arborization and soma area were previously observed in primary cultures of mesencephalic dopaminergic neurons after 3-day exposure to dopamine agonists via activation of D(3) autoreceptors (D(3) R). In this work, we showed that cocaine significantly increased dendritic arborization and soma area of dopaminergic neurons from E12.5 mouse embryos by activating phosphorylation of extracellular signal-regulated kinase (ERK) and thymoma viral proto-oncogene (Akt). These effects were dependent on functional D(3) R expression because cocaine did not produce morphological changes or ERK/Akt phosphorylation neither in primary cultures of D(3) R mutant mice nor following pharmacologic blockade with D(3) R antagonists SB-277011-A and S-33084. Cocaine effects on morphology and ERK/Akt phosphorylation were inhibited by pre-incubation with the phosphatidylinositol 3-kinase inhibitor LY294002. These observations were corroborated in vivo by morphometrical assessment of mesencephalic dopaminergic neurons of P1 newborns exposed to cocaine from E12.5 to E16.5. Cocaine increased the soma area of wild-type but not of D(3) R mutant mice, supporting the translational value of primary culture. These findings indicate a direct involvement of D3R and ERK/Akt pathways as critical mediators of cocaine-induced structural plasticity, suggesting their involvement in psychostimulant addiction.
  Journal of Neurochemistry 12/2011; 120(5):765-78. · 4.06 Impact Factor
• Source

  Available from: Arianna Bellucci

  Article: Redistribution of DAT/α-synuclein complexes visualized by "in situ" proximity ligation assay in transgenic mice modelling early Parkinson's disease.

  Arianna Bellucci, Laura Navarria, Elisa Falarti, Michela Zaltieri, Federica Bono, Ginetta Collo, Maria Grazia Spillantini, Maria Grazia, Cristina Missale, Pierfranco Spano
  [show abstract] [hide abstract]
  ABSTRACT: Alpha-synuclein, the major component of Lewy bodies, is thought to play a central role in the onset of synaptic dysfunctions in Parkinson's disease (PD). In particular, α-synuclein may affect dopaminergic neuron function as it interacts with a key protein modulating dopamine (DA) content at the synapse: the DA transporter (DAT). Indeed, recent evidence from our "in vitro" studies showed that α-synuclein aggregation decreases the expression and membrane trafficking of the DAT as the DAT is retained into α-synuclein-immunopositive inclusions. This notwithstanding, "in vivo" studies on PD animal models investigating whether DAT distribution is altered by the pathological overexpression and aggregation of α-synuclein are missing. By using the proximity ligation assay, a technique which allows the "in situ" visualization of protein-protein interactions, we studied the occurrence of alterations in the distribution of DAT/α-synuclein complexes in the SYN120 transgenic mouse model, showing insoluble α-synuclein aggregates into dopaminergic neurons of the nigrostriatal system, reduced striatal DA levels and an altered distribution of synaptic proteins in the striatum. We found that DAT/α-synuclein complexes were markedly redistributed in the striatum and substantia nigra of SYN120 mice. These alterations were accompanied by a significant increase of DAT striatal levels in transgenic animals when compared to wild type littermates. Our data indicate that, in the early pathogenesis of PD, α-synuclein acts as a fine modulator of the dopaminergic synapse by regulating the subcellular distribution of key proteins such as the DAT.
  PLoS ONE 01/2011; 6(12):e27959. · 4.09 Impact Factor
• Article: The tyrosine phosphatase Shp-2 interacts with the dopamine D(1) receptor and triggers D(1) -mediated Erk signaling in striatal neurons.

  Chiara Fiorentini, Cinzia Mattanza, Ginetta Collo, Paola Savoia, Pierfranco Spano, Cristina Missale
  [show abstract] [hide abstract]
  ABSTRACT: We report a novel mechanism for dopamine D(1) receptor (D(1) R)-mediated extracellular signal-regulated kinases (Erk) activation in rat striatum. Erk signaling depends on phosphorylation and dephosphorylation events mediated by specific kinases and phosphatases. The tyrosine phosphatase Shp-2, that is required for Erk activation by tyrosine kinase receptors, has been recently shown to regulate signaling downstream of few G protein-coupled receptors. We show that the D(1) R interacts with Shp-2, that D(1) R stimulation results in Shp-2 tyrosine phosphorylation and activation in primary striatal neuronal cultures and that D(1) R/Shp-2 interaction is required for transmitting D(1) R-dependent signaling to Erk1/2 activation. D(1) R-mediated Erk1/2 phosphorylation in cultured striatal neurons is in fact abolished by over-expression of the inactive Shp-2(C/S) mutant and by small interfering RNA-induced Shp-2 silencing. Moreover, by using selective inhibitors we show that both D(1) R-induced Shp-2 activation and Erk1/2 phosphorylation are dependent on the cyclic AMP/protein kinase A pathway and require Src. These results, which were substantiated also in transfected human embryonic kidney 293 cells, provide a novel mechanism by which to converge D(1) R signaling to the Erk pathway and suggest that Shp-2 or the D(1) R/Shp-2 interface could represent a potential drug target for disorders of dopamine transmission involving malfunctioning of D(1) R signaling.
  Journal of Neurochemistry 01/2011; 117(2):253-63. · 4.06 Impact Factor
• Article: The neurobiology of dopamine receptors: evolution from the dual concept to heterodimer complexes.

  Cristina Missale, Chiara Fiorentini, Ginetta Collo, PierFranco Spano
  [show abstract] [hide abstract]
  ABSTRACT: G protein-coupled receptors (GPCRs) have been classically thought to work as monomeric entities. The current view of their organization, however, assumes that they are part of highly organized molecular complexes, where different receptors and interacting proteins are clustered. These heteromers have peculiar pharmacological, signaling, and trafficking properties. GPCR heteromerization, raising different combinatorial possibilities, thus underlies an unexpected level of diversity within this receptor family. In this paper, we summarize recent data, reported by different research groups, suggesting that the dopamine (DA) D1 receptor forms heteromers with receptors of the same family and with structurally and functionally divergent receptors. DA D1 and D3 receptors and glutamate NMDA receptors regulate rewarding mechanisms and motivated behavior, modulate emotional and cognitive processes and regulate locomotor activity by extensive cross-talk mechanisms. Co-localization of D1 and D3 receptors and D1 and NMDA receptors in specific neuronal populations in the striatum and nucleus accumbens, moreover, suggested that their cross-talk may involve direct interactions. By using different experimental approaches various groups have, in fact, demonstrated the existence of D1-NMDA and D1-D3 heteromers, in both transfected cell systems and in the straitum, with peculiar pharmacological, signaling, and functional properties. The putative role of the D1-D3 and D1-NMDA heteromers in the physiological regulation of striatal function and in the development of motor dysfunctions will be discussed.
  Journal of Receptor and Signal Transduction Research 10/2010; 30(5):347-54. · 1.59 Impact Factor
• Article: Mouse dendritic cells express the P2X7 purinergic receptor: characterization and possible participation in antigen presentation.

  C Mutini, S Falzoni, D Ferrari, P Chiozzi, A Morelli, O R Baricordi, G Collo, P Ricciardi-Castagnoli, F Di Virgilio
  [show abstract] [hide abstract]
  ABSTRACT: Immune cells express P2 purinoceptors of the P2Y and P2X subtypes. In the present work, we show that three dendritic cell (DC) lines, D2SC/1, CB1, and FSDC, representative of immature DCs, express the P2X7 (formerly P2Z) receptor, as judged from RT-PCR amplification, reactivity to a specific antiserum, and pharmacological and functional evidence. Receptor expression is higher in FSDC cells, a cell line that is functionally more mature than D2SC/1 and CB1. From the wild-type DC population, we selected cell clones lacking the P2X7R (P2X7less). We also used a P2XR blocker, oxidized ATP, to irreversibly inhibit the P2X7R. Ability of P2X7less FSDCs or of oxidized ATP-inhibited FSDCs to stimulate Ag-specific TH lymphocytes was severely decreased although Ag endocytosis was minimally affected. During coculture with TH lymphocytes, wild-type FSDC secreted large amounts of IL-1beta. Release of this cytokine was reduced in P2X7less DCs. These data show that DCs express the P2X7 purinoceptor and suggest a correlation between P2X7R expression and Ag-presenting activity.
  The Journal of Immunology 09/1999; 163(4):1958-65. · 5.79 Impact Factor