Myocyte differentiation generates nuclear invaginations traversed by myofibrils associating with sarcomeric protein mRNAs

T. Abe
2004 Journal of Cell Science  
Introduction The nuclei of various types of cells are not always smoothsurfaced spheres or ellipsoids but are occasionally folded, grooved, convoluted or invaginated. For instance, tumorderived cell lines generally have such irregularly shaped nuclei (Hoshino, 1961; Bernhard and Granboulan, 1963) . Nuclear grooves and invaginations also occur in some non-cancerous cell lines including 3T3 and NRK cells (Fricker et al., 1997; Clubb and Locke, 1998) . The nuclear deformation is not restricted to
more » ... hese cultured cells but is detected in some cell types in vivo. The nuclei of striated and smooth muscle cells as well as those of liver cells in tissues are also convoluted or invaginated (Lane, 1965; Franke and Schinko, 1969; Bourgeois et al., 1979) . Moreover, not only animal cells but also certain plant cells such as onion epidermal cells and cultured tobacco cells have nuclear grooves and invaginations (Collings et al., 2000) . The number and nature of invaginations vary from cell type to cell type, ranging from simple invaginations to intricate branched structures that penetrate into or entirely traverse the nucleus. The occurrence of nuclear grooves and invaginations in a wide variety of cell types may imply their general functional significance. Several tumor cells including human pancreatic carcinoma MIA PaCa-2 cells have nuclear invaginations and lobules containing well-developed perinuclear rings composed of vimentin and keratin intermediate filaments (IFs) (Kamei, 1994) . These filaments run along deep invaginations in the nucleus and form closed rings around the invaginations and constrictions. Thus, these perinuclear IFs are postulated to be involved in the formation of nuclear invaginations and lobules in these cells. By contrast, human adrenal cortex carcinoma 6523 Certain types of cell both in vivo and in vitro contain invaginated or convoluted nuclei. However, the mechanisms and functional significance of the deformation of the nuclear shape remain enigmatic. Recent studies have suggested that three types of cytoskeleton, microfilaments, microtubules and intermediate filaments, are involved in the formation of nuclear invaginations, depending upon cell type or conditions. Here, we show that undifferentiated mouse C2C12 skeletal muscle myoblasts had smoothsurfaced spherical or ellipsoidal nuclei, whereas prominent nuclear grooves and invaginations were formed in multinucleated myotubes during terminal differentiation. Conversion of mouse fibroblasts to myocytes by the transfection of MyoD also resulted in the formation of nuclear invaginations after differentiation. C2C12 cells prevented from differentiation did not have nuclear invaginations, but biochemically differentiated cells without cell fusion exhibited nuclear invaginations. Thus, biochemical differentiation is sufficient for the nuclear deformation. Although vimentin markedly decreased both in the biochemically and in the terminally differentiated cells, exogenous expression of vimentin in myotubes did not rescue nuclei from the deformation. On the other hand, non-striated premyofibrils consisting of sarcomeric actinmyosin filament bundles and cross-striated myofibrils traversed the grooves and invaginations. Time-lapse microscopy showed that the preformed myofibrillar structures cut horizontally into the nuclei. Prevention of myofibril formation retarded the generation of nuclear invaginations. These results indicate that the myofibrillar structures are, at least in part, responsible for the formation of nuclear grooves and invaginations in these myocytes. mRNA of sarcomeric proteins including myosin heavy chain and α-actin were frequently associated with the myofibrillar structures running along the nuclear grooves and invaginations. Consequently, the grooves and invaginations might function in efficient sarcomeric protein mRNA transport from the nucleus along the traversing myofibrillar structures for active myofibril formation.
doi:10.1242/jcs.01574 pmid:15572409 fatcat:ffg6qn4ncvbxzexq5wmnwmmzuy