| First Author | Haqq AM | Year | 2003 |
| Journal | Biochem J | Volume | 376 |
| Issue | Pt 3 | Pages | 595-605 |
| PubMed ID | 14531729 | Mgi Jnum | J:87190 |
| Mgi Id | MGI:2683840 | Doi | 10.1042/BJ20031241 |
| Citation | Haqq AM, et al. (2003) Characterization of a novel binding partner of the melanocortin-4 receptor: attractin-like protein. Biochem J 376(Pt 3):595-605 |
| abstractText | The gene dosage effect of the MC4-R (melanocortin 4 receptor) on obesity suggests that regulation of MC4-R expression and function is critically important to the central control of energy homoeostasis. In order to identify putative MC4-R regulatory proteins, we performed a yeast two-hybrid screen of a mouse brain cDNA library using the mouse MC4-R intracellular tail (residues 303-332) as bait. We report here on one positive clone that shares 63% amino acid identity with the C-terminal part of the mouse attractin gene product, a single-transmembrane-domain protein characterized as being required for agouti signalling through the melanocortin 1 receptor. We confirmed a direct interaction between this ALP (attractin-like protein) and the C-terminus of the mouse MC4-R by glutathione S-transferase pulldown experiments, and mapped the regions involved in this interaction using N- and C-terminal truncation constructs; residues 303-313 in MC4-R and residues 1280-1317 in ALP are required for binding. ALP is highly expressed in brain, but also in heart, lung, kidney and liver. Furthermore, co-localization analyses in mice showed co-expression of ALP in cells expressing MC4-R in a number of regions known to be important in the regulation of energy homoeostasis by melanocortins, such as the paraventricular nucleus of hypothalamus and the dorsal motor nucleus of the vagus. |
