Receptor-mediated cellular entry of nuclear localizing anti-DNA antibodies via myosin 1.

Abstract

A unique subset of anti-DNA antibodies enters living cells, interacts with DNase 1, and inhibits endonuclease activity, before their nuclear localization and subsequent attenuation of apoptosis. We now report that endocytosis of these immunoglobulins is mediated by cell surface binding to brush border myosin (myosin 1). Cellular entry and internalization via this unique receptor provides initial contact for entry and sorting these immunoglobulins to translocate to the nuclear pore and enter the nucleus, interact with DNase 1 within the cytoplasm, or recycle back to the cell surface. This internalization pathway provides clues to the translocation of large proteins across cell membranes and the functional effects of intracellular antibodies on cytopathology. This is the first demonstration that brush border myosin functions as a specific cell surface receptor for internalization of large proteins. ( J. Clin. Invest. 1997. 100:25-31.)

Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis

“…We mention this because the concept that autoantibodies can penetrate living cells has been controversial but provocative. [38][39][40][41] What is still not understood is the differing rates of progression of disease in patients with apparently similar levels of IgA. It may be that there is micro-heterogeneity in the antibody response so that some molecules are more efficient in caspase activation.…”

Pbc and Ama—What Is the Connection?

“…The first is endocytosis, as seen with anti-DNA in some experimental models of SLE, in which the autoantibodies are internalized after binding to brush border myosin. 38 The second is the internalization of IgA AMA through the polymeric immunoglobulin receptor on the basal surface of the biliary epithelial cell (BEC). IgA AMA are known to be present in the bile in PBC, 39 and the secretion of IgA into the bile in humans involves active transport and translocation through the BEC cytoplasm.…”

Calreticulin, a Potential Cell Surface Receptor Involved in Cell Penetration of Anti-DNA Antibodies

“…Heparan sulfate (5-7), collagen type IV (8), fibronectin (9), and myosin 1 (10) have been proposed as cell surface Ags for anti-dsDNA Ab binding. However, it is unclear whether these molecules are able to mediate the penetration of autoantibodies and to drive them to the nucleus.…”