The Leu34Phe proCART mutation leads to cocaine- and amphetamine-regulated transcript (CART) deficiency: A possible cause for obesity in humans

Date

2006-01-01

Author

Yanık, Tülin
Kuhar, MJ
Del Giudice, EM
Loh, YP

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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 wildtype proCART in AtT-20 cells showed that it was sorted to the regulated secretory pathway, a necessity for proper processing 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.

URI

https://hdl.handle.net/11511/94036

Journal

ENDOCRINOLOGY

DOI

https://doi.org/10.1210/en.2005-0812

Collections

Department of Biology, Article

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Citation Formats

T. Yanık, M. Kuhar, E. Del Giudice, and Y. Loh, “The Leu34Phe proCART mutation leads to cocaine- and amphetamine-regulated transcript (CART) deficiency: A possible cause for obesity in humans,” ENDOCRINOLOGY, vol. 147, no. 1, pp. 39–43, 2006, Accessed: 00, 2021. [Online]. Available: https://hdl.handle.net/11511/94036.