Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Scientific Correspondence
  • Published:

CART peptide levels are altered by a mutation associated with obesity at codon 34

Molecular Psychiatry volume 9, pages 1065–1066 (2004)Cite this article

SIR—CART is a regulated neuropeptide that plays a role in many physiological processes including stress, reward and reinforcement and feeding.1, 2, 3 Recently, del Giudice et al4 described a missense mutation at codon 34 of proCART that cosegregated with severe early-onset obesity. Our findings show here for the first time that this mutation has a biochemical effect and alters CART peptide levels in cells.

The Leu34Phe mutation in proCART lies immediately adjacent to a cluster of basic amino acids and was therefore hypothesized to alter proCART processing.4 Accordingly, we characterized proCART processing using human CART cDNA constructs; one expressed a leucine (wild type) while the other expressed a phenylalanine (mutated). These cDNA constructs were transfected into corticotropic AtT20 cells, a cell line that has often been used to study peptide processing. AtT20 cells also express and process CART peptides.5, 6 Processing of overexpressed human proCART after transfection with the wild-type and mutant cDNAs was analyzed by Western blotting using an antibody (C4) raised against amino acids 66–89 of human proCART.7 This antibody detects precursor and active forms of CART peptides. Specificity of CART immunoreactivity was demonstrated by pre-absorbing the antibody with an excess of the immunizing peptide prior to the incubation with the membranes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Kuhar MJ et al. Neuropeptides 2002; 36: 1–8.

    Article  CAS  Google Scholar 

  2. Hunter RG, Kuhar MJ . Curr Drug Target CNS Neurol Disord 2003; 2: 201–205.

  3. Jaworski JN et al. J Pharmacol Exp Ther 2003; 307: 1038–1044.

  4. del Giudice EM et al. Diabetes 2001; 50: 2157–2160.

    Article  CAS  Google Scholar 

  5. Barrett P et al. J Neuroendocrinol 2001; 13: 347–352.

  6. Dominguez G, Lakatos A, Kuhar MJ . J Neuroendocrinol 2002; 80: 885–893.

  7. Kuhar MJ, Yoho LL . Synapse 1999; 33: 163–171.

    Article  CAS  Google Scholar 

  8. Dey A et al. J Biol Chem 2003; 278: 15007–15014.

  9. Koylu EO et al. J Neuroendocrinol 1997; 9: 823–833.

  10. Challis BG et al. Hum Mol Genet 2002; 11: 1997–2004.

  11. Yanik T et al. ENDO 2004. New Orleans, LA, 2004.

    Google Scholar 

Download references

Acknowledgements

This work was supported by NIH grants RR00165, DA00418 and DA15162.

Author information

Authors and Affiliations

  1. Division of Neuroscience, Yerkes National Primate Research Center of Emory University, Atlanta, GA, USA

    G Dominguez & M J Kuhar

  2. Department of Pediatrics, Second University of Naples, Naples, Italy

    E M del Giudice

Authors
  1. G Dominguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E M del Giudice
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M J Kuhar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G Dominguez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dominguez, G., del Giudice, E. & Kuhar, M. CART peptide levels are altered by a mutation associated with obesity at codon 34. Mol Psychiatry 9, 1065–1066 (2004). https://doi.org/10.1038/sj.mp.4001578

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001578

This article is cited by

Search

Advanced search

Quick links