title: Cationic amphipathic peptides accumulate sialylated proteins and lipids in the plasma membrane of eukaryotic host cells.
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.
authors: Biophysics Institute, Johannes Kepler University Linz, Altenbergerstr 69, A-4040 Linz, Austria. julian.weghuber@fh-wels.at
authors: Julian
authors: J
authors: Weghuber
authors: Michael C
authors: MC
authors: Aichinger
authors: Mario
authors: M
authors: Brameshuber
authors: Stefan
authors: S
authors: Wieser
authors: Verena
authors: V
authors: Ruprecht
authors: Birgit
authors: B
authors: Plochberger
authors: Josef
authors: J
authors: Madl
authors: Andreas
authors: A
authors: Horner
authors: Siegfried
authors: S
authors: Reipert
authors: Karl
authors: K
authors: Lohner
authors: Tamás
authors: T
authors: Henics
authors: Gerhard J
authors: GJ
authors: Schütz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002412:Cations; D002478:Cells, Cultured; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
chemical_list: D002412:Cations; D008563:Membrane Lipids; D008565:Membrane Proteins; D010455:Peptides; D019158:N-Acetylneuraminic Acid