Mechanism of Cell Penetration by Permeabilization of Late Endosomes: Interplay between a Multivalent TAT Peptide and Bis(monoacylglycero)phosphate.

Autor:	Brock DJ; Department of Biochemistry and Biophysics, Texas A&M University, Biochemistry and Biophysics Building, Room 430, 300 Olsen Boulevard, College Station, TX 77843-2128, USA., Kondow-McConaghy H; Department of Biochemistry and Biophysics, Texas A&M University, Biochemistry and Biophysics Building, Room 430, 300 Olsen Boulevard, College Station, TX 77843-2128, USA., Allen J; Department of Biochemistry and Biophysics, Texas A&M University, Biochemistry and Biophysics Building, Room 430, 300 Olsen Boulevard, College Station, TX 77843-2128, USA., Brkljača Z; Division of Organic Chemistry and Biochemistry, Rudjer Boskovic Institute, Zagreb, Croatia., Kustigian L; Department of Biochemistry and Biophysics, Texas A&M University, Biochemistry and Biophysics Building, Room 430, 300 Olsen Boulevard, College Station, TX 77843-2128, USA., Jiang M; Department of Biochemistry and Biophysics, Texas A&M University, Biochemistry and Biophysics Building, Room 430, 300 Olsen Boulevard, College Station, TX 77843-2128, USA., Zhang J; Department of Biochemistry and Biophysics, Texas A&M University, Biochemistry and Biophysics Building, Room 430, 300 Olsen Boulevard, College Station, TX 77843-2128, USA., Rye H; Department of Biochemistry and Biophysics, Texas A&M University, Biochemistry and Biophysics Building, Room 430, 300 Olsen Boulevard, College Station, TX 77843-2128, USA., Vazdar M; Division of Organic Chemistry and Biochemistry, Rudjer Boskovic Institute, Zagreb, Croatia., Pellois JP; Department of Biochemistry and Biophysics, Texas A&M University, Biochemistry and Biophysics Building, Room 430, 300 Olsen Boulevard, College Station, TX 77843-2128, USA; Department of Chemistry, Texas A&M University, College Station, TX 77843, USA. Electronic address: pellois@tamu.edu.
Jazyk:	angličtina
Zdroj:	Cell chemical biology [Cell Chem Biol] 2020 Oct 15; Vol. 27 (10), pp. 1296-1307.e5. Date of Electronic Publication: 2020 Aug 11.
DOI:	10.1016/j.chembiol.2020.07.015
Abstrakt:	Many cellular delivery reagents enter the cytosolic space of cells by escaping the lumen of endocytic organelles and, more specifically, late endosomes. The mechanisms involved in endosomal membrane permeation remain largely unresolved, which impedes the improvement of delivery agents. Here, we investigate how 3TAT, a branched analog of the cell-penetrating peptide (CPP) TAT, achieves the permeabilization of bilayers containing bis(monoacylglycero)phosphate (BMP), a lipid found in late endosomes. We establish that the peptide does not induce the leakage of individual lipid bilayers. Instead, leakage requires contact between membranes. Peptide-driven bilayer contacts lead to fusion, lipid mixing, and, critically, peptide encapsulation within proximal bilayers. Notably, this encapsulation is a distinctive property of BMP that explains the specificity of CPP's membrane leakage activity. These results therefore support a model of cell penetration that requires both BMP and the vicinity between bilayers, two features unique to BMP-rich and multivesicular late endosomes. Competing Interests: Declaration of Interests The authors declare no competing financial interests. (Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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