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

Julian Weghuber, Michael Aichinger, Mario Brameshuber, Stefan Wieser, Verena Ruprecht, Birgit Plochberger, Josef Madl, Andreas Horner, Siegfried Reipert, Karl Lohner, Tamas Henics, Gerhard Schütz

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2581-2590
Number of pages10
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1808
Issue number10
DOIs
Publication statusPublished - Oct 2011

Keywords

  • Amino Acid Sequence
  • Animals
  • Cations
  • Cells, Cultured
  • Humans
  • Membrane Lipids/chemistry
  • Membrane Proteins/chemistry
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • N-Acetylneuraminic Acid/chemistry
  • Peptides/chemistry
  • KLK
  • Sialic acids
  • Plasma membrane accumulation
  • CAMPs

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