PBC68: a nuclear pore complex protein that associates reversibly with the mitotic spindle

Using autoimmune antibodies from a patient with primary biliary cirrhosis w e have identified a 68 kDa nuclear envelope protein, termed PBC68. This pro tein is coprecipitated with a 98 kDa and a 250 kDa polypeptide and is disti nct from the nuclear lamins. Immunostaining of digitonin-permeabilized cell s indicates that PBC68 is restricted to the inner (nucleoplasmic) face of t he nuclear envelope, while indirect immunofluorescence and immunoelectron m icroscopy show that PBC68 is located on fibrillar structures emanating from the nuclear pore complex, The autoantigen is modified at early prophase an d disassembles at prometaphase concurrently with the breakdown of the nucle ar envelope. The disassembled material, instead of diffusing throughout the cytoplasm as other nucleoporins, is targeted to the mitotic spindle and re mains stably bound to it until anaphase, At telophase PBC68 is released fro m 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 envelo pe proteins are actively sorted during mitosis by transiently anchoring to spindle microtubules. Furthermore, the data suggest that specific constitue nts of pore complex are released in a stepwise fashion from their anchorage sites before becoming available for nuclear reassembly.