Cell surface nucleolin interacts with and internalizes Bothrops asper Lys49 phospholipase A2 and mediates its toxic activity

Scientific Reports
Maria Lina MassiminoF Tonello

Abstract

Phospholipases A2 are a major component of snake venoms. Some of them cause severe muscle necrosis through an unknown mechanism. Phospholipid hydrolysis is a possible explanation of their toxic action, but catalytic and toxic properties of PLA2s are not directly connected. In addition, viperid venoms contain PLA2-like proteins, which are very toxic even if they lack catalytic activity due to a critical mutation in position 49. In this work, the PLA2-like Bothrops asper myotoxin-II, conjugated with the fluorophore TAMRA, was found to be internalized in mouse myotubes, and in RAW264.7 cells. Through experiments of protein fishing and mass spectrometry analysis, using biotinylated Mt-II as bait, we found fifteen proteins interacting with the toxin and among them nucleolin, a nucleolar protein present also on cell surface. By means of confocal microscopy, Mt-II and nucleolin were shown to colocalise, at 4 °C, on cell membrane where they form Congo-red sensitive assemblies, while at 37 °C, 20 minutes after the intoxication, they colocalise in intracellular spots going from plasmatic membrane to paranuclear and nuclear area. Finally, nucleolin antagonists were found to inhibit the Mt-II internalization and toxic activity and were use...Continue Reading

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Citations

Jul 22, 2019·Toxicon : Official Journal of the International Society on Toxinology·Soledad BustilloBruno Lomonte
May 20, 2020·Seminars in Cancer Biology·Félix A Urra, Ramiro Araya-Maturana
Jul 23, 2020·International Journal of Biological Macromolecules·S C TeixeiraD S Lopes
Sep 30, 2019·Toxicon : Official Journal of the International Society on Toxinology·Barbara SpolaoreFiorella Tonello
Apr 17, 2021·Toxicon : Official Journal of the International Society on Toxinology·Sofía Vargas-ValerioJulián Fernández
May 1, 2021·Toxins·Caterina Peggion, Fiorella Tonello
Aug 9, 2021·Trends in Parasitology·Samuel Cota TeixeiraVeridiana de Melo Rodrigues

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Methods Mentioned

BETA
pull-down
confocal microscopy
pull down
pulls down
transfection
FCS
electrophoresis

Software Mentioned

MaxQuant
Leica LAS AS
Image Studio

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