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 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.
Yanase
K
K
Penn Center for Molecular Studies of Kidney Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6144, USA.
Smith
R M
RM
Puccetti
A
A
Jarett
L
L
Madaio
M P
MP
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism*; D004705:Endocytosis; D007074:Immunoglobulin G / Q000378:metabolism; D007700:Kinetics; D008114:Liver Neoplasms, Experimental; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D008969:Molecular Sequence Data; D009218:Myosins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D011956:Receptors, Cell Surface; D003850:Deoxyribonuclease I; D009218:Myosins