title: Cell-penetrating peptides recruit type A scavenger receptors to the plasma membrane for cellular delivery of nucleic acids.
abstract: Scavenger receptors (SRs) are a large family of multifunctional receptors that are involved in a range of physiologic and pathologic processes. The ability of class A scavenger receptors (SR-As) to bind anionic ligands facilitates the internalization of negatively charged cell-penetrating peptide (CPP)-nucleic acid nanocomplexes and thus makes them attractive targets for delivery of various nucleic acids. Recently, we demonstrated that SR-A3 and SR-A5 are recruited from intracellular membranes to the plasma membrane after incubation with PepFect 14-splice-switching oligonucleotide complexes. Here, we examined the mechanisms responsible for translocation of SR-As to the cell surface. We demonstrate that, in addition to nanocomplexes, some amphipathic CPPs are able to induce externalization of SR-A3 and SR-A5, and this process requires the presence of calcium ions. Furthermore, translocation of SR-A3 and SR-A5 requires activity of phosphatidylinositol-3-kinase, intact actin cytoskeleton, and the presence of serum proteins in culture medium.-Juks, C., Lorents, A., Arukuusk, P., Langel, Ü., Pooga, M. Cell-penetrating peptides recruit type A scavenger receptors to the plasma membrane for cellular delivery of nucleic acids.
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Carmen
authors.initials: C
authors.lastname: Juks
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Annely
authors.initials: A
authors.lastname: Lorents
authors.affiliation: Laboratory of Molecular Biotechnology, Institute of Technology, University of Tartu, Tartu, Estonia; and.
authors.forename: Piret
authors.initials: P
authors.lastname: Arukuusk
authors.affiliation: Laboratory of Molecular Biotechnology, Institute of Technology, University of Tartu, Tartu, Estonia; and.|Department of Neurochemistry, Stockholm University, Stockholm, Sweden.
authors.forename: Ülo
authors.initials: Ü
authors.lastname: Langel
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia; mpooga@ut.ee.
authors.forename: Margus
authors.initials: M
authors.lastname: Pooga
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D020013:Calcium Signaling; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D055666:Lipopeptides / Q000737:chemistry / Q000494:pharmacology*; D049329:Nanostructures / Q000737:chemistry; D009696:Nucleic Acids / Q000737:chemistry; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D055666:Lipopeptides; D009696:Nucleic Acids; C560878:PepFect14 peptide; D051116:Receptors, Scavenger; D019869:Phosphatidylinositol 3-Kinases
keywords: Ca2+ signaling; PI3K; SR-A3; SR-A5