RECEPTOR-MEDIATED CELLULAR ENTRY OF NUCLEAR LOCALIZING ANTI-DNA ANTIBODIES VIA MYOSIN-1

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 t hat endocytosis of these immunoglobulins is mediated by cell surface b inding to brush border myosin (myosin 1). Cellular entry and internali zation 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 recy cle back to the cell surface. This internalization pathway provides cl ues to the translocation of large proteins across cell membranes and t he functional effects of intracellular antibodies on cytopathology. Th is is the first demonstration that brush border myosin functions as a specific cell surface receptor for internalization of large proteins.