The soluble extracellular fragment of neuroligin-1 targets Aβ oligomers to the postsynaptic region of excitatory synapses

Amyloid-\u3b2 oligomers (A\u3b2o) play a major role in the synaptic dysfunction of Alzheimer's disease (AD). Neuroligins are postsynaptic cell-adhesion molecules, that share an extracellular domain with high degree of similarity to acetylcholinesterase (AChE), one of the first putative A\u3b2o receptors. We recently found that A\u3b2o interact with the soluble N-terminal fragment of neuroligin-1 (NL-1). We report here that A\u3b2o associate with NL-1 at excitatory hippocampal synapses, whereas almost no association was observed with neuroligin-2, an isoform present at inhibitory synapses. Studies using purified hippocampal postsynaptic densities indicate that NL-1 interacts with A\u3b2o in a complex with GluN2B-containing NMDA receptors. Additionally, the soluble fragment of NL-1 was used as a scavenger for A\u3b2o. Field excitatory postsynaptic potentials indicate that fragments of NL-1 protect hippocampal neurons from the impairment induced by A\u3b2o. To our knowledge, this is the first report of the interaction between this extracellular fragment of NL-1 and A\u3b2o, strongly suggest that NL-1 facilitates the targeting of A\u3b2o to the postsynaptic regions of excitatory synapses

The RNF10 protein interacts with the GluN2A subunit of the NMDA-type Glutamate receptor

Modulation of NMDA subunits composition is determinant for the biophysical properties, synaptic transmission and important for synaptic plasticity. In developing neurons NMDA GluN2B subunit is abundant, whereas mature neurons express more GluN2A subunit. Modulation of synaptic localization of GluN2A is not completely clarified, thus we explored new interaction partners for this NMDAR subunit. Through yeast two hybrid screening we found that Ring Finger Protein 10 (RNF10) interacts with GluN2A c-terminal tail. Thus, the main objective will be to study the interaction between GluN2A and RNF10 in hippocampal neurons and determinate its consequence in the synaptic function. Our data shows for first time the localization of RNF10 in hippocampal neurons, which is present in postsynaptic density. Also we found that RNF10 co-localizes with PSD-95 and preliminary data shows GluN2A, but not GluN2B, c-terminal interacts with RNF10. On the other hand we observed that RNF10 localization is modify by synaptic activity, where BCC treatments concentrate RNF10 at the nucleus. Our results suggest that RNF10 has a roll in the synaptic activity process which remain to be elucidate

Styrene, an Unpalatable Substrate with Complex Regulatory Networks

Styrene, a volatile organic compound (VOC), is an important industrial material involved in the production of plastic, synthetic rubber and resin, insulation and other industrial materials containing molecules such as polystyrene, butadiene-styrene latex, styrene copolymers and unsaturated polyester resins. Styrene exposure may cause contact-based skin inflammation, irritation of eyes, nose and respiratory tract. Neurological effects such as alterations in vision, hearing loss and longer reaction times, have been associated with styrene exposure in the workplace. In addition, styrene oxide may act as an established mutagen and carcinogen (www.epa.gov/chemfact/styre-sd.pdf). It has been reported that, in 2002, 22,323 tons of styrene were released to the environment (82), in spite of the US Clean Air Act mandate on reduction in the volume of allowable styrene emission (www.epa.gov/chemfact/styre-sd.pdf). Among a variety of emerging air pollution technologies, biofiltration is an attractive option for the treatment of VOCs, because it is cost-effective and does not generate secondary contaminants (45). Moreover, microbial biodegradation is the major route for the removal of non-aqueous compounds from soils. Styrene is also naturally present in non polluted environments, since it derives from fungal decarboxylation of cinnamic acid (90). Therefore it is not surprising that microorganisms of different families have been found to be able to degrade this compound (31). The promising results obtained in the removal of styrene from contaminated waste-gases by biofiltration (5, 39, 103) have led to an increasing attention to the regulatory mechanisms underlying styrene degradation, with the aim to improve bioremediation processes. Despite the diffusion in nature of this degradative capability, only few strains, mainly belonging to the Pseudomonas genus, have been characterized (66). This chapter is focused on the up-to-now discovered regulatory mechanisms underlying the expression of the styrene-catabolism genes. Moreover, open questions on environmental and metabolic constrains that govern styrene degradation are discussed. Biotechnological relevance of styrene-degrading strains in fine chemicals production and bioremediation processes is not examined here. Main topics on these application fields have recently been reviewed by Dobson and co-workers (66)