1,721,054 research outputs found
Constitutive TrkA activity in receptor-overexpressing PC12 clones
No full textWe have studied ligand-independent signaling by the nerve growth factor receptor TrkA in PC12 clones, under conditions of receptor overexpression. Our results indicate that TrkA-overexpressing PC12 clones display constitutive receptor activation, involving both the mature, 140-kDa form and the immature, intracellular 110-kDa form of the receptor. Phosphorylation of Tyr 674/675, located in the activation loop domain and reflecting TrkA kinase activity, appears particularly prominent in the immature form of the receptor. Constitutive receptor activation is able to chronically stimulate the PI-3 kinase/Akt as well as the mitogen-activated protein kinase pathways, leading to ligand-independent neurite extension. Under conditions of overexpression, a significant fraction of the receptor is retained intracellularly by thiol-mediated mechanisms. Exposure of the cells to reducing agents promotes translocation of the intracellular pool of the receptor to the plasma membrane and suppresses ligand-independent neurite outgrowth. Our results suggest that the levels of expression of TrkA, both intracellularly and at the cell surface, may act to modulate its kinase activity and generate ligand-independent downstream signaling. (C) 2002 Elsevier Science (USA)
The synapsins: key actors of synapse function and plasticity
No full textThe synapsins are a family of neuronal phosphoproteins evolutionarily conserved in invertebrate and vertebrate organisms. Their best-characterised function is to modulate neurotransmitter release at the presynaptic terminal, by reversibly tethering synaptic vesicles (SVs) to the actin cytoskeleton. However, many recent data have suggested novel functions for synapsins in other aspects of the presynaptic physiology, such as SV docking, fusion and recycling. Synapsin activity is tightly regulated by several protein kinases and phosphatases, which modulate the association of synapsins to SVs as well as their interaction with actin filaments and other synaptic proteins. In this context, synapsins act as a link between extracellular stimuli and the intracellular signalling events activated upon neuronal stimulation. Genetic manipulation of synapsins in various in vivo models has revealed that, although not essential for the basic development and functioning of neuronal networks, these proteins are extremely important in the fine-tuning of neuronal plasticity, as shown by the epileptic phenotype and behavioural abnormalities characterising mouse lines lacking one or more synapsin isoforms.
In this review, we summarise the current knowledge about how the various members of the synapsin family are involved in the modulation of the presynaptic physiology. We give a comprehensive description of the molecular basis of synapsin function, as well as an overview of the more recent evidence linking mutations in the synapsin proteins to the onset of severe central nervous system diseases such as epilepsy and schizophrenia
Effects of the neuronal phosphoprotein synapsin I on actin polymerization. II. Analytical interpretation of kinetic curves
No full textFluorescence resonance energy transfer detection of synaptophysin I and vesicle-associated membrane protein 2 interactions during exocytosis from single live synapses
Full text linkTranscranial direct current stimulation of the mouse prefrontal cortex modulates serotonergic neural activity of the dorsal raphe nucleus
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Specific localization of the alpha-latrotoxin receptor in the nerve terminal plasma membrane
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