Lamin complexes in the nuclear interior control progenitor cell proliferation and tissue homeostasis.
Lamins are components of the peripheral nuclear lamina that has important mechanical roles in nuclear architecture. Lamins have increasingly been implicated in nuclear processes, including DNA replication, chromatin organization and transcription. Recent data highlight the specific functions of a small pool of lamina-independent A-type lamins, located throughout the nucleoplasm, in the regulation of cell cycle progression in early tissue progenitor cells. This novel role of nucleoplasmic lamins is likely mediated by their regulatory activity towards the tumor suppressor Retinoblastoma protein. We describe how an interaction partner of A-type lamins, lamina-associated polypeptide 2alpha (LAP2alpha) affects targeting of lamins A and C to the nuclear interior and how this complex may affect cell cycle progression and tissue homeostasis. Finally, we discuss implications of these novel findings for understanding the pathogenesis of laminopathies, a group of human diseases caused by mutations in lamins.
Max F. Perutz Laboratories, Medical University of Vienna, Vienna, Austria.
Nana
N
Naetar
Roland
R
Foisner
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D034882:Lamins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D012175:Retinoblastoma / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D034882:Lamins; D008565:Membrane Proteins; C093413:lamina-associated polypeptide 2