Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

Hancock, Melissa L.; Canetta, Sarah; Role, Lorna W.; Talmage, David A.

doi:10.1083/jcb.200710037

Cited by 56 publications

(58 citation statements)

References 65 publications

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“…As α7 nAChRs are present within these enlarged boutons, and as en passant boutons are increased and enlarged upon inactivation of α7 nAChR, axonal α7 nAChRs may be an intrinsic factor within glutamatergic axons that modulates the formation of presynaptic boutons. Considerable anatomical and functional evidence supports the presence of α7 nAChRs in glutamatergic axonal terminals in different cortical regions (14,25,(33)(34)(35)(36). Thus, α7 may be a structural determinant for presynaptic development in glutamatergic synapses throughout the brain.…”

Section: Discussionmentioning

confidence: 99%

Axonal α7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons

Lin

Vicini

Hsu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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In association with NMDA receptors (NMDARs), neuronal α7 nicotinic ACh receptors (nAChRs) have been implicated in neuronal plasticity as well as neurodevelopmental, neurological, and psychiatric disorders. However, the role of presynaptic NMDARs and their interaction with α7 nAChRs in these physiological and pathophysiological events remains unknown. Here we report that axonal α7 nAChRs modulate presynaptic NMDAR expression and structural plasticity of glutamatergic presynaptic boutons during early synaptic development. Chronic inactivation of α7 nAChRs markedly increased cell surface NMDAR expression as well as the number and size of glutamatergic axonal varicosities in cortical cultures. These boutons contained presynaptic NMDARs and α7 nAChRs, and recordings from outside-out pulled patches of enlarged presynaptic boutons identified functional NMDAR-mediated currents. Multiphoton imaging of presynaptic NMDAR-mediated calcium transients demonstrated significantly larger responses in these enlarged boutons, suggesting enhanced presynaptic NMDAR function that could lead to increased glutamate release. Moreover, whole-cell patch clamp showed a significant increase in synaptic charge mediated by NMDAR miniature EPSCs but no alteration in the frequency of AMPAR miniature EPSCs, suggesting the selective enhancement of postsynaptically silent synapses upon inactivation of α7 nAChRs. Taken together, these findings indicate that axonal α7 nAChRs modulate presynaptic NMDAR expression and presynaptic and postsynaptic maturation of glutamatergic synapses, and implicate presynaptic α7 nAChR/NMDAR interactions in synaptic development and plasticity. silent synapse | synaptic development | synaptic plasticity | alpha bungarotoxin | cytisine

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Section: Discussionmentioning

confidence: 99%

Axonal α7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons

Lin

Vicini

Hsu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…[23][24][25][26] A HapMap database constructed from a GWAS has suggested a statistically significant association between the SNPs under the LD block in NRG1 and HSCR. 7 A recent validation study in the Chinese population also confirmed this disease association.…”

Section: Discussionmentioning

confidence: 99%

Association of genetic polymorphisms in the RET-protooncogene and NRG1 with Hirschsprung disease in Thai patients

et al. 2012

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Hirschsprung disease (HSCR) is a congenital developmental defect of the enteric nervous system known to be associated with the RET-protooncogene and other candidates. Recently, a genome-wide association study has added NRG1, a regulator of the development of the enteric ganglia precursors, as a new candidate gene. The aim of this study is to validate the association of the RET-protooncogene and the NRG1 in HSCR in Thai patients. The study used TaqMan single-nucleotide polymorphism (SNP) genotyping and PCR-restriction fragment length polymorphism for genotyping of 10 SNPs within the RET-protooncogene and four SNPs within the NRG1, in 68 Thai sporadic HSCR cases and 120 ethnic-matched controls. On univariate disease association analysis, 9 of 10 RET-protooncogene SNPs and all four NRG1 SNPs showed an association with HSCR. The rs2435357 (RET-protooncogene) and rs2439305 (NRG1) showed the strongest associations with the disease at P-values of 8.17E-09 (odds ratio (OR)¼6.43, 95% confidence intervals (CI)¼3.33-12.40) and 6.94E-03 (OR¼3.28, 95% CI¼1.28-8.38), respectively. The RET-protooncogene rs2435357 (TT genotype) in combination with the NRG1 rs2439305 (GG genotype) was strongly associated with an increased risk of HSCR with a P-value of 1.99E-04 (OR¼20.34, 95% CI; 2.54-162.78) when compared with a single SNP of the RET-protooncogene or NRG1. Genetic variation of the RET-protooncogene and NRG1 is involved in the risk of HSCR development in the Thai population. Moreover, the study also detected a combined effect of SNPs by SNP-SNP interaction, which may help in predicting HSCR risk.

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“…This may be explained, however, by the release from cells of the extracellular domain containing the 127 epitope and intracellular retention of the other half of the molecule containing the 123 and 128 epitopes. This latter fragment may also be biologically significant as it has been reported that intracellular fragments of NRG1 isoforms are involved in 'reverse-signalling' where they are translocated to the cell nucleus and affect gene transcription (Hancock et al 2008). It is not as yet known if any of the NRG4 isoforms can function in this way, but it is clearly a possibility as NRG4 was detected in the nuclei of salivary glands and spermatocytes (Supplementary text, see section on supplementary data given at the end of this article).…”

Section: Discussionmentioning

confidence: 99%

Expression of neuregulin 4 splice variants in normal human tissues and prostate cancer and their effects on cell motility

Hayes¹,

Blackburn²,

Boyle³

et al. 2010

Endocrine Related Cancer

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The neuregulin 4 gene encodes at least five different variants (designated A1, A2, B1, B2 and B3) produced as a result of alternative splicing. We have determined their sites of expression in normal human adult tissues using isoform-specific antibodies. Their expression is cell type specific and differs in subcellular location suggesting that they may have varied functions in these contexts. We have shown in a panel of prostate cancers that each form is present to differing degrees, and that principal component analysis indicates that there are three patterns of expression. Some isoforms were positively correlated with high prostate-specific antigen levels and others were inversely associated with Gleason score. Synthetic, refolded A forms promoted lamellipodia and filopodia formation in cells expressing the ErbB4 (CTa) receptor and stimulated cell motility in wound healing assays. The data suggest that the different forms have varied sites of expression and function, and this includes effects on cell architecture and motility.

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Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

Cited by 56 publications

References 65 publications

Axonal α7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons

Axonal α7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons

Association of genetic polymorphisms in the RET-protooncogene and NRG1 with Hirschsprung disease in Thai patients

Expression of neuregulin 4 splice variants in normal human tissues and prostate cancer and their effects on cell motility

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