Nuclear localizing anti-DNA antibodies enter living cells through specific cell surface binding to brush border myosin 1, which mediates their endocytosis and subsequent intracellular trafficking.
Brush border myosin 1 acts as a specific cell surface receptor mediating the endocytosis and subsequent nuclear localization of a unique subset of anti-DNA autoantibodies.
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.) Key words: autoimmunity systemic lupus erythematosus endocytosis cell surface receptor autoantibody Previously described methods were used for labeling Ig ( 125 I), coculture of cells with antibodies, and determination of the quantity of nuclear Ig (9). To determine if the interactive cell surface antigen was trypsin sensitive, H35 cells were grown in flasks to near confluency, harvested, and resuspended (10 7 cells/ml) in Krebs-Ringer Mops buffer containing 0.1% BSA. The cells were then incubated in the ab-
Yanase et al. (Tue,) conducted a other in Systemic lupus erythematosus. Nuclear localizing anti-DNA antibodies (H7, H72, H9) vs. MOPC-21 (isotype matched control) was evaluated on Cell surface binding and internalization via myosin 1. Nuclear localizing anti-DNA antibodies enter living cells through specific cell surface binding to brush border myosin 1, which mediates their endocytosis and subsequent intracellular trafficking.