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. 2009 Apr 14;66(11-12):1985–1997. doi: 10.1007/s00018-009-9179-2

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

J Y Jang 1, J G Jeong 1, H R Jun 1, S C Lee 2, J S Kim 3, Y S Kim 4,, M H Kwon 1,
PMCID: PMC11115804  PMID: 19373434

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.

Electronic supplementary material

The online version of this article (doi:10.1007/s00018-009-9179-2) contains supplementary material, which is available to authorized users.

Keywords. Anti-DNA antibody, 3D8 scFv, endocytosis, RNA-hydrolysis, cell death

Electronic Supplementary material

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(PDF 881 kb) (881.1KB, pdf)

Footnotes

Received 05 March 2009; accepted 20 March 2009

Contributor Information

Y. S. Kim, FAX: +82-31-219-2394, Email: kimys@ajou.ac.kr

M. H. Kwon, FAX: +82-31-219-5079, Email: kwonmh@ajou.ac.kr

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(PDF 881 kb) (881.1KB, pdf)

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