title: Nuclear substructure reorganization during late-stage erythropoiesis is selective and does not involve caspase cleavage of major nuclear substructural proteins.
abstract: Enucleation, a rare feature of mammalian differentiation, occurs in 3 cell types: erythroblasts, lens epithelium, and keratinocytes. Previous investigations suggest that caspase activation functions in lens epithelial and keratinocyte enucleation, as well as in early erythropoiesis encompassing erythroid burst-forming unit (BFU-E) differentiation to proerythroblast. To determine whether caspase activation contributes to later erythropoiesis and whether nuclear substructures other than chromatin reorganize, we analyzed distributions of nuclear subcompartment proteins and assayed for caspase-induced cleavage of subcompartmental target proteins in mouse erythroblasts. We found that patterns of lamin B in the filamentous network interacting with both the nuclear envelope and DNA, nuclear matrix protein NuMA (Nuclear mitotic apparatus), and splicing factors Sm and SC35 persisted during nuclear condensation, consistent with effective transcription of genes expressed late in differentiation. Thus, nuclear reorganization prior to enucleation is selective, allowing maintenance of critical transcriptional processes independent of extensive chromosomal reorganization. Consistent with these data, we found no evidence for caspase-induced cleavage of major nuclear subcompartment proteins during late erythropoiesis, in contrast to what has been observed in early erythropoiesis and in lens epithelial and keratinocyte differentiation. These findings imply that nuclear condensation and extrusion during terminal erythroid differentiation involve novel mechanisms that do not entail major activation of apoptotic machinery.
authors.affiliation: Life Sciences Division, University of California Lawrence Berkeley National Laboratory, Bldg 74, 1 Cyclotron Rd, Berkeley, CA 94720, USA.
authors.forename: Sharon Wald
authors.initials: SW
authors.lastname: Krauss
authors.forename: Annie J
authors.initials: AJ
authors.lastname: Lo
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Short
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Koury
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
authors.forename: Joel Anne
authors.initials: JA
authors.lastname: Chasis
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000502:physiology / Q000648:ultrastructure*; D022003:Cell Nucleus Structures / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004900:Erythroblasts / Q000648:ultrastructure; D004920:Erythropoiesis; D034921:Lamin Type B / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*
chemical_list: D034921:Lamin Type B; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D004247:DNA; D020169:Caspases