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Sphingolipid-Binding Domain in the Serotonin1A Receptor

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Biochemical Roles of Eukaryotic Cell Surface Macromolecules

Part of the book series: Advances in Experimental Medicine and Biology ((volume 749))

Abstract

Sphingolipids are essential components of eukaryotic cell membranes and are responsible for important cellular functions. A characteristic feature of sphingolipid organization in cellular membranes is their segregation in membrane domains. Serotonin1A receptors are representative members of the superfamily of G-protein coupled receptors (GPCRs) and are implicated in the generation and modulation of various cognitive, developmental, and behavioral functions. We previously reported that sphingolipids are necessary for ligand binding and cellular signaling of the human serotonin1A receptor. Proteins that interact with (glyco)sphingolipids are reported to have a characteristic amino acid sequence, termed the “sphingolipid-binding domain” (SBD). We report here that the human serotonin1A receptor contains a putative SBD, corresponding to amino acids 99 to 109. Interestingly, our analysis shows that the SBD motif appears to be an inherent feature of the serotonin1A receptor and is conserved over natural evolution across various phyla. However, experiments with the 11-mer SBD peptide in model membranes utilizing intrinsic tryptophan fluorescence did not show significant binding, probably highlighting the importance of the overall “context” of the receptor architecture in lipid–GPCR interactions. These results constitute the first report of the presence of SBD in serotonin receptors and could provide novel insight into the molecular nature of GPCR–sphingolipid interaction.

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Abbreviations

5-HT1A receptor:

5-Hydroxytryptamine-1A receptor

CRAC:

Cholesterol recognition/interaction amino acid consensus

DMPC:

Dimyristoyl-sn-glycero-3-phosphocholine

FB1 :

Fumonisin B1

GPCR:

G-protein coupled receptor

LED:

Light-emitting diode

LUV:

Large unilamellar vesicle

POPC:

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine

SBD:

Sphingolipid-binding domain

Serotonin:

5-Hydroxytryptamine

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Acknowledgments

This work was supported by the Council of Scientific and Industrial Research, India (A.C.), and Centre National de la Recherche Scientifique, France (J.F.). Y.D.P. was the recipient of a Postdoctoral Fellowship from a CSIR Network project on Nanomaterials and Nanodevices (NWP0035). P.S. thanks the Council of Scientific and Industrial Research for the award of a Senior Research Fellowship. A.C. is an Adjunct Professor at the Special Centre for Molecular Medicine of Jawaharlal Nehru University (New Delhi, India) and Indian Institute of Science Education and Research (Mohali, India), and Honorary Professor of the Jawaharlal Nehru Centre for Advanced Scientific Research (Bangalore, India). A.C. gratefully acknowledges support from J.C. Bose Fellowship (Department of Science and Technology, Govt. of India). We thank Sourav Haldar for helpful discussion and members of A.C.’s research group for critically reading the manuscript.

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Authors and Affiliations

  1. Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, 500 007, India

    Amitabha Chattopadhyay, Yamuna Devi Paila, Sandeep Shrivastava, Shrish Tiwari & Pushpendra Singh

  2. CNRS UMR 6231, University of Aix-Marseille 2 and Aix-Marseille 3, Marseille, France

    Jacques Fantini

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  1. Amitabha Chattopadhyay
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  2. Yamuna Devi Paila
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  4. Shrish Tiwari
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  5. Pushpendra Singh
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  6. Jacques Fantini
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Correspondence to Amitabha Chattopadhyay or Jacques Fantini .

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Editors and Affiliations

  1. Riverside Transit Campus, School of Biological Sciences, Central University of Kerala, Kasargod, 671328, Kerala, India

    Perumana R. Sudhakaran

  2. National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, Delhi, India

    Avadhesha Surolia

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Chattopadhyay, A., Paila, Y.D., Shrivastava, S., Tiwari, S., Singh, P., Fantini, J. (2012). Sphingolipid-Binding Domain in the Serotonin1A Receptor. In: Sudhakaran, P., Surolia, A. (eds) Biochemical Roles of Eukaryotic Cell Surface Macromolecules. Advances in Experimental Medicine and Biology, vol 749. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3381-1_19

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