ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
A common single nucleotide polymorphism alters the synthesis and secretion of neuropeptide Y.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Cargo receptor Surf4 regulates endoplasmic reticulum export of proinsulin in pancreatic β-cells.Communications biology · 2022Article
- Current Insights Into the Role of Neuropeptide Y in Skin Physiology and Pathology.Frontiers in endocrinology · 2022Review
- Conditional Inactivation of Limbic Neuropeptide Y-1 Receptors Increases Vulnerability to Diet-Induced Obesity in Male Mice.International journal of molecular sciences · 2021Article
- A role for NPY-NPY2R signaling in albuminuric kidney disease.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The RareCells · 2020Article
- NPY and Gene Therapy for Epilepsy: How, When,... and Y.Frontiers in molecular neuroscience · 2020Review
- Multiple gas-phase conformations of proline-containing peptides: is it always cis/trans isomerization?The Analyst · 2016Article
- Stress-induced changes in adrenal neuropeptide Y expression are regulated by a negative feedback loop.Journal of neurochemistry · 2013Article
- Comparison of the dipeptidyl peptidase-4 gene methylation levels between severely obese subjects with and without the metabolic syndrome.Diabetology & metabolic syndrome · 2013Article
- The regulated secretory pathway and human disease: insights from gene variants and single nucleotide polymorphisms.Frontiers in endocrinology · 2013Article
- Neuropeptide Y in the noradrenergic neurons induces the development of cardiometabolic diseases in a transgenic mouse model.Indian journal of endocrinology and metabolism · 2012Article
- Activation of NPY type 5 receptors induces a long-lasting increase in spontaneous GABA release from cerebellar inhibitory interneurons.Journal of neurophysiology · 2012Article
- Diet-induced obesity in mice overexpressing neuropeptide y in noradrenergic neurons.International journal of peptides · 2012Article
- Polymorphisms in the neuropeptide Y gene and the risk of obesity: findings from two prospective cohorts.The Journal of clinical endocrinology and metabolism · 2011Article
- Cell type-dependent trafficking of neuropeptide Y-containing dense core granules in CNS neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Pancreatic beta cells synthesize neuropeptide Y and can rapidly release peptide co-transmitters.PloS one · 2011Article
- Neuropeptide Y gene functional polymorphism influences susceptibility to hypertension in Indian population.Journal of human hypertension · 2010Article
- Neuropeptide Y gene polymorphisms are not associated with obesity in a South Indian population.European journal of clinical nutrition · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
A single nucleotide polymorphism (SNP) in the neuropeptide Y gene has been associated with elevated serum lipid levels and cardiovascular disease. The polymorphism (T1128C) changes the seventh amino acid in the prohormone from leucine to proline. It has been speculated this alters neuropeptide Y (NPY) synthesis, trafficking, or secretion. We tested this hypothesis by expressing the mutant and wild-type prohormones in CNS neurons and endocrine cells. Synthesis and trafficking were followed using immunocytochemistry and fluorescent protein-tagged fusion constructs. Mutant prohormone was synthesized and entered the regulated secretory pathway. When expressed in endocrine cells, wild-type and mutant proteins were found in the same large dense core granules. However, the T1128C polymorphism altered the degree of copackaging, and, on average, individual granules contained more mutant prohormone. This was not attributable to codon bias but to the change in prohormone sequence. Global prohormone targeting was normal, because in hippocampal neurons, the polarized distribution of the mutant prohormone was indistinguishable from the wild-type. When secretion was measured from chromaffin cells, brief depolarizations triggered peptide secretion, confirming the entry of the mutant prohormone into the regulated secretory pathway. However, cells that expressed the mutant protein had increased levels of peptide secretion. We conclude that the T1128C polymorphism alters the packaging and secretion of NPY. In contrast to SNPs in other prohormones, we could not find a phenotype until the prohormone was tracked at the single granule level. These results are consistent with studies showing the T1128C polymorphism has pleiotropic effects.
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