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Signaling together apart

Distinct latrophilin halves (red and green) wander away from each other. USHKARYOV

After being cleaved apart, two halves of a split personality receptor protein are free to wander far away from each other, say Kirill Volynski, Yuri Ushkaryov, and colleagues (Imperial College, London, UK). But when signaling is needed the two halves reunite.

The receptor, called latrophilin, is known only as a binding site for the black widow poison latrotoxin. Although no endogenous ligand for latrophilin is known, a varied family of receptors exists with a similar organization. Each family member has two domains: an NH₂-terminal fragment (NTF) that interacts with other cell surface or possibly extracellular matrix proteins, and a COOH-terminal fragment (CTF) that resembles a G-protein–coupled receptor (GPCR). The two domains were known to be cleaved, but the persistence of the NTF on the cell surface led previous workers to assume that the transmembrane-less NTF must remain bound to CTF.

The London group now shows that this is not the case. The two fragments have distinct localizations and can be aggregated away from each other using antibodies. Addition of a latrotoxin variant, however, induces clustering of the fragments and signaling.

For the cell, the fusion of two protein functions allows for coordinated expression, but cleavage allows divergent regulation. For example, the NTF may stay attached extracellularly even as the CTF is internalized to allow for GPCR desensitization. Ushkaryov now hopes to test whether different members of the protein family mix and match their respective halves.

Reference:

Volynski, K.E., et al. 2004. EMBO J. doi:10.1038/sj.embo.7600443.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 854K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?