PBC68: a nuclear pore complex protein that associates reversibly with the mitotic spindle.
Using autoimmune antibodies from a patient with primary biliary cirrhosis we have identified a 68 kDa nuclear envelope protein, termed PBC68. This protein is co-precipitated with a 98 kDa and a 250 kDa polypeptide and is distinct from the nuclear lamins. Immunostaining of digitonin-permeabilized cells indicates that PBC68 is restricted to the inner (nucleoplasmic) face of the nuclear envelope, while indirect immunofluorescence and immunoelectron microscopy show that PBC68 is located on fibrillar structures emanating from the nuclear pore complex. The autoantigen is modified at early prophase and disassembles at prometaphase concurrently with the breakdown of the nuclear envelope. The disassembled material, instead of diffusing throughout the cytoplasm as other nucleoporins, is targeted to the mitotic spindle and remains stably bound to it until anaphase. At telophase PBC68 is released from the mitotic apparatus and reassembles late, after incorporation of LAP2B and B-type lamins, onto the reforming nuclear envelope. The partitioning of PBC68 in dividing cells supports the notion that subsets of nuclear envelope proteins are actively sorted during mitosis by transiently anchoring to spindle microtubules. Furthermore, the data suggest that specific constituents of pore complex are released in a stepwise fashion from their anchorage sites before becoming available for nuclear reassembly.
Theodoropoulos
P A
PA
Department of Basic Sciences and Department of Internal Medicine, The University of Crete, School of Medicine, Crete, Greece. georgato@med.uoc.gr
Polioudaki
H
H
Koulentaki
M
M
Kouroumalis
E
E
Georgatos
S D
SD
D001324:Autoantigens / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000276:immunology; D016253:Microscopy, Immunoelectron; D008970:Molecular Weight; D009685:Nuclear Envelope / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001324:Autoantigens; D009687:Nuclear Proteins