Extraordinary structural diversity of NPY-family receptors

Molecular clones are a prerequisite for detailed characterization of all proteins, particularly for receptors, which are often difficult to purify owing to their hydrophobic nature. A DNA clone not only allows production of its encoded receptor in cultured cells for detailed pharmacological characterization but it can also be used as a probe to determine the receptor s mRNA distribution in the body. The specificity of such probes is usually much greater than for antisera, especially if the protein belongs to a multi-member family because an antiserum may cross-react with related proteins. Other possibilities offered by molecular clones are transgenic animals and gene-disrupted animals, which can provide in vivo data on receptor functions. 

The molecular cloning of receptors that bind to neuropeptide Y (NPY) and its related peptides, peptide YY (PYY) and pancreatic polypeptide (PP), has advanced somewhat more slowly than for many other peptide receptors. Even after the Y1 receptor was cloned (Herzog et al., 1992 Krause et al., 1992 Larhammar et al., 1992) progress has been modest despite expectations from pharmacological studies for up to six more receptor genes, i.e. receptor-types Y2 and Y3 as well as receptors for appetite , PYY, PP and PP-fold peptides. At last, reports from several laboratories described clones for additional receptor subtypes, namely the Y2 receptor and a PP receptor, also called Y4 (see Table 1 for all sequence accession codes). The long wait is 

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Subtype Species Accession code Accession code Reference 

YFGPLCF1F1CV FKI VI AlKRRNHnnDICnAOHICYASSETKRINI — 1 1LLSIUUAFAUCULPLTIFHTUFO l 1 UHHQIIRTCNHNL 1 LFLLCHLTRniSTCUNPIFVCFl 1 NKHFQR 

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