42 337

Cited 0 times in

A nucleic acid-hydrolyzing antibody penetrates into cells via caveolae-mediated endocytosis, localizes in the cytosol and exhibits cytotoxicity.

Authors
Jang, JY; Jeong, JG; Jun, HR; Lee, SC; Kim, JS; Kim, YS; Kwon, MH
Citation
Cellular and molecular life sciences : CMLS, 66(11-12):1985-1997, 2009
Journal Title
Cellular and molecular life sciences : CMLS
ISSN
1420-682X1420-9071
Abstract
Many natural anti-DNA antibodies (Abs) have the ability to translocate across the plasma membrane and localize in the nucleus of mammalian cells, frequently leading to cytotoxicity to cells. Herein, we report detailed intracellular trafficking routes and cytotoxicity in HeLa cells for a single chain variable fragment (scFv) Ab, 3D8, which is an anti-DNA Ab capable of hydrolyzing both DNA and RNA. The intracellular penetration of 3D8 scFv occurred by caveolae/lipid raft endocytosis. The time-course chasing experiments revealed that 3D8 scFv escaped directly from the caveosome into the cytosol and remained in the cytosol without further trafficking into endosomes, lysosomes, endoplasmic reticulum, Golgi, or nucleus. The cytosolically localized 3D8 scFv maintained its nuclease activity to hydrolyze cellular RNAs, mainly mRNAs, eventually triggering apoptotic cell death. Our results demonstrate that 3D8 scFv has a unique intracellular trafficking route of localizing in the cytosol, thereby exhibiting cytotoxicity due to its nuclease activity.
MeSH terms
Antibodies, Antinuclear/metabolism*Antibodies, Antinuclear/pharmacologyApoptosisCaveolae/physiology*Cell Membrane PermeabilityCell Survival/drug effectsCytosol/metabolism*EndocytosisHela CellsHumansHydrolysisImmunoglobulin Variable Region/metabolism*Immunoglobulin Variable Region/pharmacologyMembrane MicrodomainsProteoglycans/metabolismRNA/metabolismRibonucleases/metabolism
DOI
10.1007/s00018-009-9179-2
PMID
19373434
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
권, 명희
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse