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Papers by Giulia Pregno
Frontiers in Cellular Neuroscience, 2011
GABAergic synapses exhibit a high degree of subcellular and molecular specialization, which contr... more GABAergic synapses exhibit a high degree of subcellular and molecular specialization, which contrasts with their apparent simplicity in ultrastructural appearance. Indeed, when observed in the electron microscope, GABAergic synapses fit in the symmetric, or Gray's type II category, being characterized by a relatively simple postsynaptic specialization. The inhibitory postsynaptic density cannot be readily isolated, and progress in understanding its molecular composition has lagged behind that of excitatory synapses. However, recent studies have brought significant progress in the identification of new synaptic proteins, revealing an unexpected complexity in the molecular machinery that regulates GABAergic synaptogenesis. In this article, we provide an overview of the molecular diversity of GABAergic synapses, and we consider how synapse specificity may be encoded by selective trans-synaptic interactions between pre-and postsynaptic adhesion molecules and secreted factors that reside in the synaptic cleft. We also discuss the importance of developing cataloguing tools that could be used to decipher the molecular diversity of synapses and to predict alterations of inhibitory transmission in the course of neurological diseases.
Frontiers in Cellular Neuroscience, 2013
Neurexins (Nrxs) have emerged as potential determinants of synaptic specificity, but little is kn... more Neurexins (Nrxs) have emerged as potential determinants of synaptic specificity, but little is known about their localization at central synapses. Here we show that Nrxs have a remarkably selective localization at distinct types of glutamatergic synapses and we reveal an unexpected ontogenetic regulation of Nrx expression at GABAergic synapses. Our data indicate that synapses are specified by molecular interactions that involve both Nrx-dependent and Nrx-independent mechanisms. We propose that differences in the spatio-temporal profile of Nrx expression may contribute to specify the molecular identity of synapses.
BMC Neuroscience, 2011
Background: A number of studies have separately shown that the neuregulin1 (NRG1)/ErbB4 system an... more Background: A number of studies have separately shown that the neuregulin1 (NRG1)/ErbB4 system and NMDAtype glutamate receptors (NMDARs) are involved in several aspects of neuronal migration. In addition, intracellular calcium fluctuations play central roles in neuronal motility. Stable expression of the tyrosine kinase receptor ErbB4 promotes migratory activity in the neural progenitor cell line ST14A upon NRG1 stimulation. In this work we analyzed the potential interactions between the NRG1/ErbB4 system and NMDARs in the ST14A migratory process as well as its calcium dependence. Results: RT-PCR studies have shown that both native ST14A cells (non-expressing ErbB4), as well as ErbB4transfected cells express low levels of a restricted number of NMDAR subunits: NR1, NR2C, NR2D and NR3B. The resulting NMDAR would form Ca 2+ channels characterized by low Mg 2+ -sensitivity and low Ca 2+ -permeability, generating small, long-lasting currents. Ca 2+ -imaging experiments showed slow [Ca 2+ ] i increases in 45% of the cells following 8 μM NMDA stimulation. Basal migration of ErbB4-transfected ST14A cells was unaffected by 18 hrs NMDA incubation. However, over the same incubation time, NMDA was able to significantly enhance NRG1induced migration. Pre-incubation with the intracellular calcium chelator BAPTA-AM reduced both NRG1-and NRG1/NMDA-stimulated migration, suggesting the involvement of Ca 2+ in these processes. NRG1 stimulation of ErbB4-transfected ST14A cells induced a sustained, long-lasting increase in [Ca 2+ ] i , in 99% of the cells. These intracellular Ca 2+ signals could be ascribed to both release from intracellular stores and influx from the extracellular medium trough a mechanism of store-operated calcium entry (SOCE). Short-time co-incubation of NMDA and NRG1 did not substantially modify the NRG1-induced intracellular calcium signals. Conclusions: In summary, NRG1 stimulation of the ErbB4 receptor exerts a sustained [Ca 2+ ] i increase in ST14A neural progenitors; NRG1-induced migration is Ca 2+ -dependent and can be positively modulated by activation of the NMDA receptor.
Frontiers in Cellular Neuroscience, 2011
GABAergic synapses exhibit a high degree of subcellular and molecular specialization, which contr... more GABAergic synapses exhibit a high degree of subcellular and molecular specialization, which contrasts with their apparent simplicity in ultrastructural appearance. Indeed, when observed in the electron microscope, GABAergic synapses fit in the symmetric, or Gray's type II category, being characterized by a relatively simple postsynaptic specialization. The inhibitory postsynaptic density cannot be readily isolated, and progress in understanding its molecular composition has lagged behind that of excitatory synapses. However, recent studies have brought significant progress in the identification of new synaptic proteins, revealing an unexpected complexity in the molecular machinery that regulates GABAergic synaptogenesis. In this article, we provide an overview of the molecular diversity of GABAergic synapses, and we consider how synapse specificity may be encoded by selective trans-synaptic interactions between pre-and postsynaptic adhesion molecules and secreted factors that reside in the synaptic cleft. We also discuss the importance of developing cataloguing tools that could be used to decipher the molecular diversity of synapses and to predict alterations of inhibitory transmission in the course of neurological diseases.
Frontiers in Cellular Neuroscience, 2013
Neurexins (Nrxs) have emerged as potential determinants of synaptic specificity, but little is kn... more Neurexins (Nrxs) have emerged as potential determinants of synaptic specificity, but little is known about their localization at central synapses. Here we show that Nrxs have a remarkably selective localization at distinct types of glutamatergic synapses and we reveal an unexpected ontogenetic regulation of Nrx expression at GABAergic synapses. Our data indicate that synapses are specified by molecular interactions that involve both Nrx-dependent and Nrx-independent mechanisms. We propose that differences in the spatio-temporal profile of Nrx expression may contribute to specify the molecular identity of synapses.
BMC Neuroscience, 2011
Background: A number of studies have separately shown that the neuregulin1 (NRG1)/ErbB4 system an... more Background: A number of studies have separately shown that the neuregulin1 (NRG1)/ErbB4 system and NMDAtype glutamate receptors (NMDARs) are involved in several aspects of neuronal migration. In addition, intracellular calcium fluctuations play central roles in neuronal motility. Stable expression of the tyrosine kinase receptor ErbB4 promotes migratory activity in the neural progenitor cell line ST14A upon NRG1 stimulation. In this work we analyzed the potential interactions between the NRG1/ErbB4 system and NMDARs in the ST14A migratory process as well as its calcium dependence. Results: RT-PCR studies have shown that both native ST14A cells (non-expressing ErbB4), as well as ErbB4transfected cells express low levels of a restricted number of NMDAR subunits: NR1, NR2C, NR2D and NR3B. The resulting NMDAR would form Ca 2+ channels characterized by low Mg 2+ -sensitivity and low Ca 2+ -permeability, generating small, long-lasting currents. Ca 2+ -imaging experiments showed slow [Ca 2+ ] i increases in 45% of the cells following 8 μM NMDA stimulation. Basal migration of ErbB4-transfected ST14A cells was unaffected by 18 hrs NMDA incubation. However, over the same incubation time, NMDA was able to significantly enhance NRG1induced migration. Pre-incubation with the intracellular calcium chelator BAPTA-AM reduced both NRG1-and NRG1/NMDA-stimulated migration, suggesting the involvement of Ca 2+ in these processes. NRG1 stimulation of ErbB4-transfected ST14A cells induced a sustained, long-lasting increase in [Ca 2+ ] i , in 99% of the cells. These intracellular Ca 2+ signals could be ascribed to both release from intracellular stores and influx from the extracellular medium trough a mechanism of store-operated calcium entry (SOCE). Short-time co-incubation of NMDA and NRG1 did not substantially modify the NRG1-induced intracellular calcium signals. Conclusions: In summary, NRG1 stimulation of the ErbB4 receptor exerts a sustained [Ca 2+ ] i increase in ST14A neural progenitors; NRG1-induced migration is Ca 2+ -dependent and can be positively modulated by activation of the NMDA receptor.