title: Sorting nexin 6 enhances lamin a synthesis and incorporation into the nuclear envelope.
abstract: 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.
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: González-Granado
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Navarro-Puche
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Molina-Sanchez
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Blanco-Berrocal
authors.affiliation: Instituto de Biomedicina de Valencia (IBV), Consejo Superior de Investigaciones Científicas, Valencia, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Viana
authors.affiliation: Fundación para la Investigación Hospital La Fe, and Instituto Valenciano de Patología, Facultad de Medicina, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Font de Mora
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Andrés
mesh_terms: D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000096:biosynthesis*; D051379:Mice; D009685:Nuclear Envelope / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D021381:Protein Transport; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058305:Sorting Nexins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism
chemical_list: D034904:Lamin Type A; D012333:RNA, Messenger; C431150:SNX6 protein, human; C532245:SNX6 protein, mouse; D058305:Sorting Nexins; D046988:Proteasome Endopeptidase Complex; D020931:ran GTP-Binding Protein