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The Leu34Phe ProCART mutation leads to cocaine- and amphetamine-regulated transcript (CART) deficiency: a possible cause for obesity in humans
- Publication Year :
- 2006
-
Abstract
- Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic neuropeptide synthesized in the hypothalamus. A Leu34Phe missense mutation in proCART has been found in an obese family in humans. Here we show that humans bearing the Leu34Phe mutation in proCART have severely diminished levels of bioactive CART, but elevated amounts of partially processed proCART in their serum. Expression of wild-type proCART in AtT-20 cells showed that it was sorted to the regulated secretory pathway, a necessity for proper processing to bioactive CART. However, expressed Leu34Phe proCART was missorted, poorly processed, and secreted constitutively. The defective intracellular sorting of Leu34Phe proCART would account for the reduced levels of bioactive CART in affected humans. These results suggest that the obesity observed in humans bearing the Leu34Phe mutation could be due to a putative deficiency in hypothalamic bioactive CART.
- Subjects :
- Male
Cart
medicine.medical_specialty
Mutation, Missense
Neuropeptide
Nerve Tissue Proteins
Transfection
medicine.disease_cause
Cocaine and amphetamine regulated transcript
Cell Line
Endocrinology
Internal medicine
medicine
Humans
Missense mutation
Obesity
Amphetamine
Secretory pathway
Mutation
business.industry
Recombinant Proteins
Amino Acid Substitution
nervous system
Mutagenesis, Site-Directed
Female
business
hormones, hormone substitutes, and hormone antagonists
Intracellular
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....cb917407cc8459c78ddf3cdcd9a802c3