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Sorting Nexin 6 Enhances Lamin A Synthesis and Incorporation into the Nuclear Envelope

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...

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Autores principales: González-Granado, Jose M., Navarro-Puche, Ana, Molina-Sanchez, Pedro, Blanco-Berrocal, Marta, Viana, Rosa, de Mora, Jaime Font, Andrés, Vicente
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275242/
https://www.ncbi.nlm.nih.gov/pubmed/25535984
http://dx.doi.org/10.1371/journal.pone.0115571
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author González-Granado, Jose M.
Navarro-Puche, Ana
Molina-Sanchez, Pedro
Blanco-Berrocal, Marta
Viana, Rosa
de Mora, Jaime Font
Andrés, Vicente
author_facet González-Granado, Jose M.
Navarro-Puche, Ana
Molina-Sanchez, Pedro
Blanco-Berrocal, Marta
Viana, Rosa
de Mora, Jaime Font
Andrés, Vicente
author_sort González-Granado, Jose M.
collection PubMed
description 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.
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spelling pubmed-42752422014-12-31 Sorting Nexin 6 Enhances Lamin A Synthesis and Incorporation into the Nuclear Envelope González-Granado, Jose M. Navarro-Puche, Ana Molina-Sanchez, Pedro Blanco-Berrocal, Marta Viana, Rosa de Mora, Jaime Font Andrés, Vicente PLoS One Research Article 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. Public Library of Science 2014-12-23 /pmc/articles/PMC4275242/ /pubmed/25535984 http://dx.doi.org/10.1371/journal.pone.0115571 Text en © 2014 González-Granado et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
González-Granado, Jose M.
Navarro-Puche, Ana
Molina-Sanchez, Pedro
Blanco-Berrocal, Marta
Viana, Rosa
de Mora, Jaime Font
Andrés, Vicente
Sorting Nexin 6 Enhances Lamin A Synthesis and Incorporation into the Nuclear Envelope
title Sorting Nexin 6 Enhances Lamin A Synthesis and Incorporation into the Nuclear Envelope
title_full Sorting Nexin 6 Enhances Lamin A Synthesis and Incorporation into the Nuclear Envelope
title_fullStr Sorting Nexin 6 Enhances Lamin A Synthesis and Incorporation into the Nuclear Envelope
title_full_unstemmed Sorting Nexin 6 Enhances Lamin A Synthesis and Incorporation into the Nuclear Envelope
title_short Sorting Nexin 6 Enhances Lamin A Synthesis and Incorporation into the Nuclear Envelope
title_sort sorting nexin 6 enhances lamin a synthesis and incorporation into the nuclear envelope
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275242/
https://www.ncbi.nlm.nih.gov/pubmed/25535984
http://dx.doi.org/10.1371/journal.pone.0115571
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