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Involvement of the Lamin Rod Domain in Heterotypic Lamin Interactions Important for Nuclear Organization

The nuclear lamina is a meshwork of intermediate-type filament proteins (lamins) that lines the inner nuclear membrane. The lamina is proposed to be an important determinant of nuclear structure, but there has been little direct testing of this idea. To investigate lamina functions, we have characte...

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Detalles Bibliográficos
Autores principales: Schirmer, Eric C., Guan, Tinglu, Gerace, Larry
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190570/
https://www.ncbi.nlm.nih.gov/pubmed/11331300
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author Schirmer, Eric C.
Guan, Tinglu
Gerace, Larry
author_facet Schirmer, Eric C.
Guan, Tinglu
Gerace, Larry
author_sort Schirmer, Eric C.
collection PubMed
description The nuclear lamina is a meshwork of intermediate-type filament proteins (lamins) that lines the inner nuclear membrane. The lamina is proposed to be an important determinant of nuclear structure, but there has been little direct testing of this idea. To investigate lamina functions, we have characterized a novel lamin B1 mutant lacking the middle ∼4/5 of its α-helical rod domain. Though retaining only 10 heptads of the rod, this mutant assembles into intermediate filament-like structures in vitro. When expressed in cultured cells, it concentrates in patches at the nuclear envelope. Concurrently, endogenous lamins shift from a uniform to a patchy distribution and lose their complete colocalization, and nuclei become highly lobulated. In vitro binding studies suggest that the internal rod region is important for heterotypic associations of lamin B1, which in turn are required for proper organization of the lamina. Accompanying the changes in lamina structure induced by expression of the mutant, nuclear pore complexes and integral membrane proteins of the inner membrane cluster, principally at the patches of endogenous lamins. Considered together, these data indicate that lamins play a major role in organizing other proteins in the nuclear envelope and in determining nuclear shape.
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spelling pubmed-21905702008-05-01 Involvement of the Lamin Rod Domain in Heterotypic Lamin Interactions Important for Nuclear Organization Schirmer, Eric C. Guan, Tinglu Gerace, Larry J Cell Biol Original Article The nuclear lamina is a meshwork of intermediate-type filament proteins (lamins) that lines the inner nuclear membrane. The lamina is proposed to be an important determinant of nuclear structure, but there has been little direct testing of this idea. To investigate lamina functions, we have characterized a novel lamin B1 mutant lacking the middle ∼4/5 of its α-helical rod domain. Though retaining only 10 heptads of the rod, this mutant assembles into intermediate filament-like structures in vitro. When expressed in cultured cells, it concentrates in patches at the nuclear envelope. Concurrently, endogenous lamins shift from a uniform to a patchy distribution and lose their complete colocalization, and nuclei become highly lobulated. In vitro binding studies suggest that the internal rod region is important for heterotypic associations of lamin B1, which in turn are required for proper organization of the lamina. Accompanying the changes in lamina structure induced by expression of the mutant, nuclear pore complexes and integral membrane proteins of the inner membrane cluster, principally at the patches of endogenous lamins. Considered together, these data indicate that lamins play a major role in organizing other proteins in the nuclear envelope and in determining nuclear shape. The Rockefeller University Press 2001-04-30 /pmc/articles/PMC2190570/ /pubmed/11331300 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Schirmer, Eric C.
Guan, Tinglu
Gerace, Larry
Involvement of the Lamin Rod Domain in Heterotypic Lamin Interactions Important for Nuclear Organization
title Involvement of the Lamin Rod Domain in Heterotypic Lamin Interactions Important for Nuclear Organization
title_full Involvement of the Lamin Rod Domain in Heterotypic Lamin Interactions Important for Nuclear Organization
title_fullStr Involvement of the Lamin Rod Domain in Heterotypic Lamin Interactions Important for Nuclear Organization
title_full_unstemmed Involvement of the Lamin Rod Domain in Heterotypic Lamin Interactions Important for Nuclear Organization
title_short Involvement of the Lamin Rod Domain in Heterotypic Lamin Interactions Important for Nuclear Organization
title_sort involvement of the lamin rod domain in heterotypic lamin interactions important for nuclear organization
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190570/
https://www.ncbi.nlm.nih.gov/pubmed/11331300
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