A novel effect of PDLIM5 in α7 nicotinic acetylcholine receptor upregulation and surface expression.

Nicotinic acetylcholine receptors (nAChRs) are widespread throughout the central nervous system. Signaling through nAChRs contributes to numerous higher-order functions, including memory and cognition, as well as abnormalities such as nicotine addiction and neurodegenerative disorders. Although recent studies indicate that the PDZ-containing proteins comprising PSD-95 family co-localize with nicotinic acetylcholine receptors and mediate downstream signaling in the neurons, the mechanisms by which α7nAChRs are regulated remain unclear. Here, we show that the PDZ-LIM domain family protein PDLIM5 binds to α7nAChRs and plays a role in nicotine-induced α7nAChRs upregulation and surface expression. We find that chronic exposure to 1 µM nicotine upregulated α7, ß2-contained nAChRs and PDLIM5 in cultured hippocampal neurons, and the upregulation of α7nAChRs and PDLIM5 is increased more on the cell membrane than the cytoplasm. Interestingly, in primary hippocampal neurons, α7nAChRs and ß2nAChRs display distinct patterns of expression, with α7nAChRs colocalized more with PDLIM5. Furthermore, PDLIM5 interacts with α7nAChRs, but not ß2nAChRs in native brain neurons. Knocking down of PDLIM5 in SH-SY5Y abolishes nicotine-induced upregulation of α7nAChRs. In primary hippocampal neurons, using shRNA against PDLIM5 decreased both surface clustering of α7nAChRs and α7nAChRs-mediated currents. Proteomics analysis and isothermal titration calorimetry (ITC) results show that PDLIM5 interacts with α7nAChRs through the PDZ domain, and the interaction between PDLIM5 and α7nAChRs can be promoted by nicotine. Collectively, our data suggest a novel cellular role of PDLIM5 in the regulation of α7nAChRs, which may be relevant to plastic changes in the nervous system.

Prenatal diagnosis of Meier-Gorlin syndrome 7: a case presentation.

BACKGROUND: Meier-Gorlin syndrome 7 (MGS7) is a rare autosomal recessive condition. We reported a fetus diagnosed with Meier-Gorlin syndrome 7. The antenatal sonographic images were presented, and compound heterozygous mutations of CDC45 on chromosome 22 were identified by whole-exome sequencing (WES). CASE PRESENTATION: Fetal growth restriction (FGR), craniosynostosis, and brachydactyly of right thumb were found in a fetus of 28th gestational weeks. The fetus was diagnosed as MGS7 clinically. After extensive counseling, the couple opted for prenatal diagnosis by cordocentesis and termination of pregnancy. Karyotype analysis and WES were performed. Chromosomal karyotyping showed that the fetus was 46, XY. There were 2 mutations of CDC45, the causal gene of MGS7 on chromosome 22, which were inherited from the couple respectively were identified by WES. Facial dysmorphism, brachydactyly of right thumb, and genitalia abnormally were proved by postpartum autopsy, and craniosynostosis was confirmed by three-dimensional computed tomography (3D-CT) reconstruction. CONCLUSIONS: It is possible to detect multiple clinical features of Meier-Gorlin syndrome in prenatal sonography. Deteriorative FGR complicated with craniosynostosis indicates MGS7. Combination of 2D and 3D ultrasonography helps to detect craniosynostosis. The affected fetus was confirmed a compound heterozygote of CDC45 related MGS by whole-exome sequencing, which is critical in identifying rare genetic diseases.

Nicotine recruits glutamate receptors to postsynaptic sites.

Cholinergic neurons project throughout the nervous system and activate nicotinic receptors to modulate synaptic function in ways that shape higher order brain function. The acute effects of nicotinic signaling on long-term synaptic plasticity have been well-characterized. Less well understood is how chronic exposure to low levels of nicotine, such as those encountered by habitual smokers, can alter neural connections to promote addiction and other lasting behavioral effects. We show here that chronic exposure of hippocampal neurons in culture to low levels of nicotine recruits AMPA and NMDA receptors to the cell surface and sequesters them at postsynaptic sites. The receptors include GluA2-containing AMPA receptors, which are responsible for most of the excitatory postsynaptic current mediated by AMPA receptors on the neurons, and include NMDA receptors containing GluN1 and GluN2B subunits. Moreover, we find that the nicotine treatment also increases expression of the presynaptic component synapsin 1 and arranges it in puncta juxtaposed to the additional AMPA and NMDA receptor puncta, suggestive of increases in synaptic contacts. Consistent with increased synaptic input, we find that the nicotine treatment leads to an increase in the excitatory postsynaptic currents mediated by AMPA and NMDA receptors. Further, the increases skew the ratio of excitatory-to-inhibitory input that the cell receives, and this holds both for pyramidal neurons and inhibitory neurons in the hippocampal CA1 region. The GluN2B-containing NMDA receptor redistribution at synapses is associated with a significant increase in GluN2B phosphorylation at Tyr1472, a site known to prevent GluN2B endocytosis. These results suggest that chronic exposure to low levels of nicotine not only alters functional connections but also is likely to change excitability levels across networks. Further, it may increase the propensity for synaptic plasticity, given the increase in synaptic NMDA receptors.

[Expression of aquaporins 1, 3, 8, 9 mRNA in human fetal membranes].

OBJECTIVE: To investigate the expression of aquaporin (AQP)-1, 3, 8, 9 in human fetal membrane and their role in the human amniotic fluid circulation. METHODS: RT-PCR was employed for detection of the expressions of AQP-1, 3, 8, 9 mRNA in human amnion and chorion from 20 women with normal term pregnancy. RESULTS: AQP-1, 3, 8, 9 mRNA expression was detected in both human amnion and chorion, and no significant difference was found in their expression levels or between the amnion and chorion (P>0.05). CONCLUSION: AQP-1, 3, 8, 9 can be associated with intramembranous transport and volume regulation of amniotic fluid.