The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity
Open accessAbstract
Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans 1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity 4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity in humans.
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“NPY also has an important role in the central regulation of food intake and energy expenditure 181.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [181]
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“A specific ventromedial hypothalamus deletion resulted in the same effect (301), although a different subregion of the hypothalamus, the paraventricular nucleus, has also been implicated in the body weight regulation of AC3 (302).”
From Physiological roles of mammalian transmembrane adenylyl cyclase isoforms (2022) · cites this paper as [302]
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Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030
The primary cilium: a signalling centre during vertebrate development
Goetz, S. C., & Anderson, K. V. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2774 · Cited by 1,824
Genes and molecular pathways underpinning ciliopathies
Reiter, J. F., & Leroux, M. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.60 · Cited by 1,588
Self-citationVertebrate Smoothened functions at the primary cilium
Corbit, K. C., Aanstad, P., Singla, V., Norman, A. R., Stainier, D. Y. R., & Reiter, J. F. (2005) · Nature · doi:10.1038/nature04117 · Cited by 1,481
Self-citationHildebrandt, F., Benzing, T., & Katsanis, N. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1010172 · Cited by 1,331
Divergence of Melanocortin Pathways in the Control of Food Intake and Energy Expenditure
Balthasar, N., Dalgaard, L. T., Lee, C. E., Yu, J. H., Funahashi, H., Williams, T. B., Ferreira, M. A. R., Tang, V., McGovern, R. A., Kenny, C. D., et al. (2005) · Cell · doi:10.1016/j.cell.2005.08.035 · Cited by 1,107
A frameshift mutation in human MC4R is associated with a dominant form of obesity
Vaisse, C., Clément, K., Guy-grand, B., & Froguel, P. (1998) · Nature Genetics · doi:10.1038/2407 · Cited by 1,091
Self-citationMelanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity
Vaisse, C., Clement, K., Durand, E., Hercberg, S., Guy-Grand, B., & Froguel, P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9238 · Cited by 897
Self-citationNeurobiology of food intake in health and disease
Morton, G. J., Meek, T. H., & Schwartz, M. W. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3745 · Cited by 748
Davenport, J. R., Watts, A. J., Roper, V. C., Croyle, M. J., van Groen, T., Wyss, J. M., Nagy, T. R., Kesterson, R. A., & Yoder, B. K. (2007) · Current Biology · doi:10.1016/j.cub.2007.08.034 · Cited by 482
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The genetics of obesity: From discovery to biology
Loos, R. J. F., & Yeo, G. S. H. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00414-z · Cited by 1,291
Cellular signalling by primary cilia in development, organ function and disease
Anvarian, Z., Mykytyn, K., Mukhopadhyay, S., Pedersen, L. B., & Christensen, S. T. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0116-9 · Cited by 845
Mechanisms of signalling and biased agonism in G protein-coupled receptors
Wootten, D. L., Christopoulos, A., Martí-Solano, M., Babu, M. M., & Sexton, P. M. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0049-3 · Cited by 764
Establishing and regulating the composition of cilia for signal transduction
Nachury, M. V., & Mick, D. U. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0116-4 · Cited by 397
CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency
Matharu, N., Rattanasopha, S., Tamura, S., Maliskova, L., Wang, Y., Bernard, A., Hardin, A., Eckalbar, W. L., Vaisse, C., & Ahituv, N. (2019) · Science · doi:10.1126/science.aau0629 · Cited by 323
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Metadata
- Authors
- Siljee, J. E., Wang, Y., Bernard, A. A., Ersoy, B. A., Zhang, S., Marley, A., Von Zastrow, M., Reiter, J. F., & Vaisse, C.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Vaisse, Christian
- Venue
- Nature Genetics
- Published
- 2018-01-08
- Volume
- 50
- Issue
- 2
- Pages
- 180-185
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC5805646
- OpenAlex
- W2781875842
- Cited by
- 247
- References
- 30
- Citations by year
- 2026: 24 · 2025: 30 · 2024: 27 · 2023: 22 · 2022: 25 · 2021: 40 · 2020: 33 · 2019: 22 · 2018: 24
- FWCI
- 18.21
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Drug Abuse (P01DA010154, R01DA010711, R01DA012864)
- National Institute of General Medical Sciences (R01GM095941)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK098722, R01DK060540, P30DK063720, R01DK106404)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR054396)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- melanocortin-4 receptor, ADCY3, primary cilia, obesity, leptin-melanocortin pathway, hypothalamic neurons, ciliopathies, adenylyl cyclase signaling, genetic predisposition to obesity, body weight, receptor subcellular localization
- MeSH terms
- Adenylyl Cyclases, Animals, Cells, Cultured, Cilia, Female, Humans, Male, Mice, Transgenic, Mutation, Neurons, Obesity, Signal Transduction, Genetic Predisposition to Disease, NIH 3T3 Cells, Intracellular Space, Receptor, Melanocortin, Type 4, Mice, HEK293 Cells
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