Sorting nexin 6 enhances lamin a synthesis and incorporation into the nuclear envelope

• Published in: PloS one Vol. 9; no. 12; p. e115571
• Main Authors: González-Granado, Jose M, Navarro-Puche, Ana, Molina-Sanchez, Pedro, Blanco-Berrocal, Marta, Viana, Rosa, Font de Mora, Jaime, Andrés, Vicente
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.12.2014; Public Library of Science (PLoS)
• Subjects: Alzheimer's disease; Animals; Biology and Life Sciences; Cell cycle; Cell Line; Cells (Biology); Cofactors; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endosomes - metabolism; Epidemiology; Epidermal growth factor; Gene expression; Guanosine triphosphate; Homeostasis; Humans; Intermediate filament proteins; Kinases; Lamin Type A - biosynthesis; Lamins; Mammalian cells; Mice; Nexin; Nuclear Envelope - metabolism; Nuclear transport; Nuclei; Penicillin; Plasmids; Proteasome Endopeptidase Complex - metabolism; Protein Binding; Protein Biosynthesis; Protein Transport; Proteins; Proteolysis; ran GTP-Binding Protein - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Signal transduction; Sorting Nexins - metabolism; Structure-function relationships; Subcellular Fractions - metabolism; Synthesis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0115571

Nuclear lamins are important structural and functional proteins in mammalian cells, but little is known about the mechanisms and cofactors that regulate their traffic into the nucleus. Here, we demonstrate that trafficking of lamin A, but not lamin B1, and its assembly into the nuclear envelope are regulated by sorting nexin 6 (SNX6), a major component of the retromer that targets proteins and other molecules to specific subcellular locations. SNX6 interacts with lamin A in vitro and in vivo and links it to the outer surface of the endoplasmic reticulum in human and mouse cells. SNX6 transports its lamin A cargo to the nuclear envelope in a process that takes several hours. Lamin A protein levels in the nucleus augment or decrease, respectively, upon gain or loss of SNX6 function. We further show that SNX6-dependent lamin A nuclear import occurs across the nuclear pore complex via a RAN-GTP-dependent mechanism. These results identify SNX6 as a key regulator of lamin A synthesis and incorporation into the nuclear envelope.