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Cell‐penetrating peptides recruit type A scavenger receptors to the plasma membrane for cellular delivery of nucleic acids
Author(s) -
Juks Carmen,
Lorents Annely,
Arukuusk Piret,
Langel Ülo,
Pooga Margus
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600811r
Subject(s) - scavenger receptor , nucleic acid , internalization , chemistry , receptor , microbiology and biotechnology , biochemistry , cell membrane , cell penetrating peptide , intracellular , cell , biophysics , biology , lipoprotein , cholesterol
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. FASEB J. 31, 975–988 (2017). www.fasebj.org