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Referee Comments: Referee 1 (Roland Seifert)

Posted by PLOS_ONE_Group on 28 Dec 2007 at 18:45 GMT

Reviewer 1's Review

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The Conklin lab has pioneered the field of RASSL development, i.e. receptors soley activated by synthetic ligands. The present paper provides an excellent extension of this work, using the 5-HT4R as model system. The authors develop 5-HT4Rs with different degrees of constitutive activity and G-protein- and ligand-selectivity. The new RASSLs will certainly be of great value for the in vivo analysis of constitutive GPCR activity. The paper is very clearly written, and also discusses certain limitations of the RASSL technique.

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N.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.