Dynamic relocation of nuclear proteins during the execution phase of apoptosis

Abstract

In the apoptotic program of controlled cell dismantling, the most characteristic nuclear changes involve chromatin, which condenses and often collapses against the nuclear envelope in the form of crescents. A severe reorganization also occurs in ribonucleoprotein (RNP)-containing structures which are involved in the synthesis and processing of transcripts: already during early apoptosis, the nucleoplasmic RNPs (namely, perichromatin fibrils, perichromatin granules, and interchromatin granules) coalesce in the interchromatin space where they associate with segregated nucleolar components, to ectopically form fibro-granular heterogeneous clusters. This was found to occur in cell systems in vivo and in cultured cell lines, after different apoptogenic stimuli. These RNP aggregates we have called heterogeneous ectopic RNP-derived structures (HERDS) move from the nucleus to the cytoplasm, and may be found in apoptotic bodies, in late apoptosis. Immunolabeling experiments demonstrated that several other proteins which are normally located inside the nucleus also move into the cytoplasm, during apoptosis, independently from HERDS. Apoptotic cells have been suggested to be a powerful source of nuclear auto-antigens, which are produced by the partial proteolytic or nucleolytic cleavage of a wide variety of nuclear substrates. In the presence of defective phagocytosis (or when massive apoptosis overwhelms the clearance capability of the tissue scavenger cells), the disposal of apoptotic cells becomes insufficient and unphagocytosed late apoptotic cells may accumulate in the tissue where they may be engulfed by antigen-presenting cells (such as dendritic cells); an autoimmune response may thus be elicited, by which apoptosis-derived auto-antigens are recognized and presented to the immune system.