Cellular Uptake of A Taurine-Modified, Ester Bond-Decorated D-Peptide Derivative Via Dynamin-Based Endocytosis and Macropinocytosis

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2018 Feb 4

PMID 29396265

Citations 6

Authors

Jie Zhou

Xuewen Du

Cristina Berciu

Steven J Del Signore

Xiaoyi Chen

Natsuko Yamagata

Avital A Rodal

Daniela Nicastro

Bing Xu

Affiliations

Soon will be listed here.

Abstract

Most of the peptides used for promoting cellular uptake bear positive charges. In our previous study, we reported an example of taurine (bearing negative charges in physiological conditions) promoting cellular uptake of D-peptides. Taurine, conjugated to a small D-peptide via an ester bond, promotes the cellular uptake of this D-peptide. Particularly, intracellular carboxylesterase (CES) instructs the D-peptide to self-assemble and to form nanofibers, which largely disfavors efflux and further enhances the intracellular accumulation of the D-peptide, as supported by that the addition of CES inhibitors partially impaired cellular uptake of this molecule in mammalian cell lines. Using dynamin 1, 2, and 3 triple knockout (TKO) mouse fibroblasts, we demonstrated that cells took up this molecule via macropinocytosis and dynamin-dependent endocytosis. Imaging of Drosophila larval blood cells derived from endocytic mutants confirmed the involvement of multiple endocytosis pathways. Electron microscopy (EM) indicated that the precursors can form aggregates on the cell surface to facilitate the cellular uptake via macropinocytosis. EM also revealed significantly increased numbers of vesicles in the cytosol. This work provides new insights into the cellular uptake of taurine derivative for intracellular delivery and self-assembly of D-peptides.

Citing Articles

Recent progress in quantitative analysis of self-assembled peptides.

Cai X, Xu W, Ren C, Zhang L, Zhang C, Liu J Exploration (Beijing). 2024; 4(4):20230064.

PMID: 39175887 PMC: 11335468. DOI: 10.1002/EXP.20230064.

Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma.

Song S, Xia X, Qi J, Hu X, Chen Q, Liu J Drug Deliv. 2021; 28(1):2480-2494.

PMID: 34766543 PMC: 8592591. DOI: 10.1080/10717544.2021.2000677.

Biomaterials based on noncovalent interactions of small molecules.

Guo J, Tian C, Xu B EXCLI J. 2020; 19:1124-1140.

PMID: 33088250 PMC: 7573174. DOI: 10.17179/excli2020-2656.

Enzymatic Noncovalent Synthesis.

He H, Tan W, Guo J, Yi M, Shy A, Xu B Chem Rev. 2020; 120(18):9994-10078.

PMID: 32812754 PMC: 7530130. DOI: 10.1021/acs.chemrev.0c00306.

Specific Aptamer-Based Probe for Analyzing Biomarker MCP Entry Into Singapore Grouper Iridovirus-Infected Host Cells via Clathrin-Mediated Endocytosis.

Yu Q, Liu M, Wu S, Wei X, Xiao H, Yi Y Front Microbiol. 2020; 11:1206.

PMID: 32636813 PMC: 7318552. DOI: 10.3389/fmicb.2020.01206.

References

Ferguson S, Ferguson S, Raimondi A, Paradise S, Shen H, Mesaki K . Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits. Dev Cell. 2010; 17(6):811-22. PMC: 2861561. DOI: 10.1016/j.devcel.2009.11.005. View

Kaplan I, Wadia J, Dowdy S . Cationic TAT peptide transduction domain enters cells by macropinocytosis. J Control Release. 2005; 102(1):247-53. DOI: 10.1016/j.jconrel.2004.10.018. View

Park R, Shen H, Liu L, Liu X, Ferguson S, De Camilli P . Dynamin triple knockout cells reveal off target effects of commonly used dynamin inhibitors. J Cell Sci. 2013; 126(Pt 22):5305-12. PMC: 3828596. DOI: 10.1242/jcs.138578. View

Li J, Shi J, Medina J, Zhou J, Du X, Wang H . Selectively Inducing Cancer Cell Death by Intracellular Enzyme-Instructed Self-Assembly (EISA) of Dipeptide Derivatives. Adv Healthc Mater. 2017; 6(15). PMC: 5550337. DOI: 10.1002/adhm.201601400. View

Zorko M, Langel U . Cell-penetrating peptides: mechanism and kinetics of cargo delivery. Adv Drug Deliv Rev. 2005; 57(4):529-45. DOI: 10.1016/j.addr.2004.10.010. View

Mastronarde D . Automated electron microscope tomography using robust prediction of specimen movements. J Struct Biol. 2005; 152(1):36-51. DOI: 10.1016/j.jsb.2005.07.007. View

Hirose H, Takeuchi T, Osakada H, Pujals S, Katayama S, Nakase I . Transient focal membrane deformation induced by arginine-rich peptides leads to their direct penetration into cells. Mol Ther. 2012; 20(5):984-93. PMC: 3345973. DOI: 10.1038/mt.2011.313. View

Berg K, Selbo P, Prasmickaite L, Tjelle T, Sandvig K, Moan J . Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. Cancer Res. 1999; 59(6):1180-3. View

Gupta A, Mandal D, Ahmadibeni Y, Parang K, Bothun G . Hydrophobicity drives the cellular uptake of short cationic peptide ligands. Eur Biophys J. 2011; 40(6):727-36. DOI: 10.1007/s00249-011-0685-4. View

10.

Riggs-Gelasco P, Price J, Guyer R, Brehm J, Barr E, Bollinger Jr J . EXAFS spectroscopic evidence for an Fe=O unit in the Fe(IV) intermediate observed during oxygen activation by taurine:alpha-ketoglutarate dioxygenase. J Am Chem Soc. 2004; 126(26):8108-9. DOI: 10.1021/ja048255q. View

11.

Zhou J, Du X, Berciu C, He H, Shi J, Nicastro D . Enzyme-Instructed Self-Assembly for Spatiotemporal Profiling of the Activities of Alkaline Phosphatases on Live Cells. Chem. 2017; 1(2):246-263. PMC: 5380920. DOI: 10.1016/j.chempr.2016.07.003. View

12.

Koles K, Yeh A, Rodal A . Tissue-specific tagging of endogenous loci in Drosophila melanogaster. Biol Open. 2015; 5(1):83-9. PMC: 4728311. DOI: 10.1242/bio.016089. View

13.

Calnan B, Biancalana S, Hudson D, Frankel A . Analysis of arginine-rich peptides from the HIV Tat protein reveals unusual features of RNA-protein recognition. Genes Dev. 1991; 5(2):201-10. DOI: 10.1101/gad.5.2.201. View

14.

Duchardt F, Fotin-Mleczek M, Schwarz H, Fischer R, Brock R . A comprehensive model for the cellular uptake of cationic cell-penetrating peptides. Traffic. 2007; 8(7):848-66. DOI: 10.1111/j.1600-0854.2007.00572.x. View

15.

Del Signore S, Rodal A . The membrane strikes back: phosphoinositide binding regulates Skywalker function. Nat Struct Mol Biol. 2016; 23(11):956-957. DOI: 10.1038/nsmb.3313. View

16.

Price J, Barr E, Glass T, Krebs C, Bollinger Jr J . Evidence for hydrogen abstraction from C1 of taurine by the high-spin Fe(IV) intermediate detected during oxygen activation by taurine:alpha-ketoglutarate dioxygenase (TauD). J Am Chem Soc. 2003; 125(43):13008-9. DOI: 10.1021/ja037400h. View

17.

Maiolo 3rd J, Ottinger E, Ferrer M . Specific redistribution of cell-penetrating peptides from endosomes to the cytoplasm and nucleus upon laser illumination. J Am Chem Soc. 2004; 126(47):15376-7. DOI: 10.1021/ja044867z. View

18.

Del Signore S, Biber S, Lehmann K, Heimler S, Rosenfeld B, Eskin T . dOCRL maintains immune cell quiescence by regulating endosomal traffic. PLoS Genet. 2017; 13(10):e1007052. PMC: 5656325. DOI: 10.1371/journal.pgen.1007052. View

19.

Deshpande M, Rodal A . The Crossroads of Synaptic Growth Signaling, Membrane Traffic and Neurological Disease: Insights from Drosophila. Traffic. 2015; 17(2):87-101. DOI: 10.1111/tra.12345. View

20.

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T . Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9(7):676-82. PMC: 3855844. DOI: 10.1038/nmeth.2019. View