Cloning, Distribution and Functional Expression of the Human mGlu6 Metabotropic Glutamate Receptor
Section snippets
Isolation of cloned receptor cDNAs
A human retinal cDNA library and a human whole brain library (5 × 105 plaques) (Clontech), both constructed in the bacteriophage λgt10, were screened for human mGlu receptor cDNAs. Fragments of the rat mGlu4 receptor cDNA (kindly donated by Professor Nakanishi, Kyoto, Japan), obtained by NcoI and KpnI/SphI digestions, were internally radiolabelled by random priming (Boehringer Mannheim) using [α-32P]dCTP (Amersham) to a specific activity of 2 × 109 c.p.m./μg and used as probes. Positively
RESULTS
The deduced amino acid sequence of hmGlu6 is presented in Fig. 1, in comparison to the rat mGlu6 receptor and the human mGlu4 receptor, cloned here in parallel. The hmGlu6 receptor is a protein of 877 residues which shows 93.5% sequence identity to the rat mGlu6 sequence. The similarity increases to 96.1% when conservative substitutions are allowed. The region of greatest diversity is found within the proposed signal peptide sequence. Other differences are scattered throughout the receptor
DISCUSSION
We have cloned the human mGlu6 metabotropic glutamate receptor, which shares high sequence identity (93.5%) with its rat homologue, and reasonably high identity (69.8%) with the related human mGlu4 receptor, cloned in parallel (Fig. 1). The serine and threonine residues essential for high affinity for l-glutamate (O'Hara et al., 1993) are conserved (Fig. 1), as are many cysteine residues found in all mGlu receptors cloned to date (see Pin and Duvoisin, 1995). These cysteine residues presumably
Acknowledgements
The authors are indebted to Mr A. Wanner for excellent sequencing, and Mr I. Bobirnac for quality cAMP measurements.
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