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Evidence that prokineticin receptor 2 exists as a dimer in vivo

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An Erratum to this article was published on 03 June 2011

Abstract

Prokineticins are proteins that regulate diverse biological processes including gastrointestinal motility, angiogenesis, circadian rhythm, and innate immune response. Prokineticins bind two closed related G-protein coupled receptors (GPCRs), PKR1 and PKR2. In general, these receptors act as molecular switches to relay activation to heterotrimeric G-proteins and a growing body of evidence points to the fact that GPCRs exist as homo- or heterodimers. We show here by Western-blot analysis that PKR2 has a dimeric structure in neutrophils. By heterologous expression of PKR2 in Saccharomyces cerevisiae, we examined the mechanisms of intermolecular interaction of PKR2 dimerization. The potential involvement of three types of mechanisms was investigated: coiled-coil, disulfide bridges, and hydrophobic interactions between transmembrane domains. Characterization of differently deleted or site-directed PKR2 mutants suggests that dimerization proceeds through interactions between transmembrane domains. We demonstrate that co-expressing binding-deficient and signaling-deficient forms of PKR2 can re-establish receptor functionality, possibly through a domain-swapping mechanism.

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Abbreviations

GPCR:

G-protein coupled receptor

TMD:

Transmembrane domain

PKR:

Prokineticin receptor

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Acknowledgments

We are grateful to Dr. Addison D. Ault, Princeton University (USA), for providing the Cy12946 yeast strain and plasmid Cp1021. This work was supported in part by grants from the University of Rome La Sapienza.

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Authors and Affiliations

  1. Dipartimento di Scienze Biochimiche ‘A. Rossi Fanelli’, Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Sara Marsango, Maria Carmela Bonaccorsi di Patti, Donatella Barra & Rossella Miele

  2. Istituto Pasteur-Fondazione Cenci Bolognetti, CNR Istituto di Biologia e Patologia Molecolari, Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Donatella Barra & Rossella Miele

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  1. Sara Marsango
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  2. Maria Carmela Bonaccorsi di Patti
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Correspondence to Rossella Miele.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s00018-011-0741-3

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Marsango, S., Bonaccorsi di Patti, M.C., Barra, D. et al. Evidence that prokineticin receptor 2 exists as a dimer in vivo. Cell. Mol. Life Sci. 68, 2919–2929 (2011). https://doi.org/10.1007/s00018-010-0601-6

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