title: Nesprin-3 connects plectin and vimentin to the nuclear envelope of Sertoli cells but is not required for Sertoli cell function in spermatogenesis.
abstract: Nesprin-3 is a nuclear envelope protein that connects the nucleus to intermediate filaments by interacting with plectin. To investigate the role of nesprin-3 in the perinuclear localization of plectin, we generated nesprin-3-knockout mice and examined the effects of nesprin-3 deficiency in different cell types and tissues. Nesprin-3 and plectin are coexpressed in a variety of tissues, including peripheral nerve and muscle. The expression level of nesprin-3 in skeletal muscle is very low and decreases during myoblast differentiation in vitro. Of interest, plectin was concentrated at the nuclear envelope in only a few cell types. This was most prominent in Sertoli cells of the testis, in which nesprin-3 is required for the localization of both plectin and vimentin at the nuclear perimeter. Testicular morphology and the position of the nucleus in Sertoli cells were normal, however, in the nesprin-3-knockout mice and the mice were fertile. Furthermore, nesprin-3 was not required for the polarization and migration of mouse embryonic fibroblasts. Thus, although nesprin-3 is critical for the localization of plectin to the nuclear perimeter of Sertoli cells, the resulting link between the nuclear envelope and the intermediate filament system seems to be dispensable for normal testicular morphology and spermatogenesis.
authors.affiliation: Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Ketema
authors.forename: Maaike
authors.initials: M
authors.lastname: Kreft
authors.forename: Pablo
authors.initials: P
authors.lastname: Secades
authors.forename: Hans
authors.initials: H
authors.lastname: Janssen
authors.forename: Arnoud
authors.initials: A
authors.lastname: Sonnenberg
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development; D032446:Myoblasts / Q000502:physiology; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000502:physiology*; D009928:Organ Specificity; D051190:Plectin / Q000378:metabolism*; D021381:Protein Transport; D012708:Sertoli Cells / Q000502:physiology*; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology; D014746:Vimentin / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; C495333:Plec protein, mouse; D051190:Plectin; D014746:Vimentin; C507800:nesprin-3 protein, mouse