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Effect of Membrane Composition on Receptor Association: Implications of Cancer Lipidomics on ErbB Receptors

Abstract

The association of single transmembrane receptors, such as the ErbB receptors is a key event in initiating cell signaling networks. The interactions between these receptors have been well characterized for both ligand-driven and pre-formed dimers. However, the role of the membrane in modulating association is less well understood and assumes greater importance in light of altered membrane composition in diseased states. Here, we discuss how membrane composition has been observed to induce both structural and dynamic differences in receptor association. Computational studies, especially those using coarse-grain simulations have been successful in predicting the role of the membrane and calculating the related free energy landscapes. Membrane perturbations and differences in lipid chain order, related to the lipophobic effect, have been shown to play a large role in driving membrane protein association. Further, we review lipid compositions reported in diseased conditions and its effect on transmembrane receptor association, focusing on the ErbB growth factor receptor dimers in cancer. Understanding the role of the membrane in receptor association will provide general design principles driving receptor organization, as well as help to identify novel therapeutic strategies.

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Abbreviations

DPPC:

1,2-dipalmitoyl phosphatidylcholine

PC:

Phosphatidylcholines

SM:

Sphingomyelin

GM:

Gangliosides

PE:

Phosphatidylethanolamine

PS:

Phosphatidylserine

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Acknowledgements

This work was supported by the Ramalingaswami Fellowship (Govt. of India) and Science and Engineering Research Board (Govt. of India) project (EMR/2016/002294) to D.S. We thank Vikas Dubey and Xavier Prasanna for helpful discussions and members of our research group for critically reading the manuscript. ABP thanks the council for scientific and industrial research (CSIR), India for the senior research fellowship.

Funding

This study was funded by the Science and Engineering Research Board (Govt. of India) project (EMR/2016/002294). ABP thanks the council for scientific and industrial research (CSIR), India for the senior research fellowship.

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Correspondence to Durba Sengupta.

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Pawar, A.B., Sengupta, D. Effect of Membrane Composition on Receptor Association: Implications of Cancer Lipidomics on ErbB Receptors. J Membrane Biol 251, 359–368 (2018). https://doi.org/10.1007/s00232-018-0015-1

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Keywords

  • Lipophobic effect
  • ErbB transmembrane association
  • MARTINI simulations