Cationic amphipathic peptides accumulate sialylated proteins and lipids in the plasma membrane of eukaryotic host cells

J. Weghuber, M. Aichinger, M. Brameshuber, S. Wieser, V. Ruprecht, B. Plochberger, J. Madl, A. Horner, S. Reipert, K. Lohner, T. Henics, G. Schuetz, Biochimica et Biophysica Acta (BBA) - Biomembranes 1808 (2011) 2581–2590.

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Abstract
Cationic antimicrobial peptides (CAMPs) selectively target bacterial membranes by electrostatic interactions with negatively charged lipids. It turned out that for inhibition of microbial growth a high CAMP membrane concentration is required, which can be realized by the incorporation of hydrophobic groups within the peptide. Increasing hydrophobicity, however, reduces the CAMP selectivity for bacterial over eukaryotic host membranes, thereby causing the risk of detrimental side-effects. In this study we addressed how cationic amphipathic peptides—in particular a CAMP with Lysine–Leucine–Lysine repeats (termed KLK)—affect the localization and dynamics of molecules in eukaryotic membranes. We found KLK to selectively inhibit the endocytosis of a subgroup of membrane proteins and lipids by electrostatically interacting with negatively charged sialic acid moieties. Ultrastructural characterization revealed the formation of membrane invaginations representing fission or fusion intermediates, in which the sialylated proteins and lipids were immobilized. Experiments on structurally different cationic amphipathic peptides (KLK, 6-MO-LF11-322 and NK14-2) indicated a cooperation of electrostatic and hydrophobic forces that selectively arrest sialylated membrane constituents.
Publishing Year
Date Published
2011-10-01
Journal Title
Biochimica et Biophysica Acta (BBA) - Biomembranes
Acknowledgement
This work was funded by the GEN-AU project of the Austrian Research Promotion Agency, the Austrian Science Fund (FWF; project Y250-B03) and Intercell AG. We thank the following colleagues for providing plasmids and cells: Daniel Legler (University of Konstanz, Switzerland), Jennifer Lippincott-Schwartz (NIH, Bethesda, USA), Hannes Stockinger (Medical University Vienna, Austria), Katharina Strub (University of Geneva, Switzerland), Lawrence Rajendran (ETH Zurich, Switzerland), Eileen M. Lafer (UTHSC San Antonio, Texas, USA), Mark McNiven (Mayo Clinic, Minnesota, USA), John Silvius (McGill University, Montreal, Canada), Christoph Romanin (JKU Linz, Austria), Herbert Stangl (Medical University Vienna, Austria) and Anton van der Merwe (Oxford University, Oxford, UK). We thank Harald Kotisch (MFPL, Vienna) for excellent technical assistance in the processing of samples for electron microscopy and Sergio Grinstein (Hospital for Sick Children Research Institute, Toronto) for fruitful discussions.
Volume
1808
Issue
10
Page
2581 - 2590
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Weghuber J, Aichinger M, Brameshuber M, et al. Cationic amphipathic peptides accumulate sialylated proteins and lipids in the plasma membrane of eukaryotic host cells. Biochimica et Biophysica Acta (BBA) - Biomembranes. 2011;1808(10):2581-2590. doi:10.1016/j.bbamem.2011.06.007
Weghuber, J., Aichinger, M., Brameshuber, M., Wieser, S., Ruprecht, V., Plochberger, B., … Schuetz, G. (2011). Cationic amphipathic peptides accumulate sialylated proteins and lipids in the plasma membrane of eukaryotic host cells. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1808(10), 2581–2590. https://doi.org/10.1016/j.bbamem.2011.06.007
Weghuber, Julian, Michael Aichinger, Mario Brameshuber, Stefan Wieser, Verena Ruprecht, Birgit Plochberger, Josef Madl, et al. “Cationic Amphipathic Peptides Accumulate Sialylated Proteins and Lipids in the Plasma Membrane of Eukaryotic Host Cells.” Biochimica et Biophysica Acta (BBA) - Biomembranes 1808, no. 10 (2011): 2581–90. https://doi.org/10.1016/j.bbamem.2011.06.007.
J. Weghuber et al., “Cationic amphipathic peptides accumulate sialylated proteins and lipids in the plasma membrane of eukaryotic host cells,” Biochimica et Biophysica Acta (BBA) - Biomembranes, vol. 1808, no. 10, pp. 2581–2590, 2011.
Weghuber J, Aichinger M, Brameshuber M, Wieser S, Ruprecht V, Plochberger B, Madl J, Horner A, Reipert S, Lohner K, Henics T, Schuetz G. 2011. Cationic amphipathic peptides accumulate sialylated proteins and lipids in the plasma membrane of eukaryotic host cells. Biochimica et Biophysica Acta (BBA) - Biomembranes. 1808(10), 2581–2590.
Weghuber, Julian, et al. “Cationic Amphipathic Peptides Accumulate Sialylated Proteins and Lipids in the Plasma Membrane of Eukaryotic Host Cells.” Biochimica et Biophysica Acta (BBA) - Biomembranes, vol. 1808, no. 10, Elsevier, 2011, pp. 2581–90, doi:10.1016/j.bbamem.2011.06.007.

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