Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery

BACKGROUND: Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified. RESULTS: To search for such proteins twenty three nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells. CONCLUSIONS: The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.Publisher PDFPeer reviewe

Nesprin isoforms: are they inside or outside the nucleus?

Abstract The giant isoforms of nesprins 1 and 2 are emerging as important players in cellular organization, particularly in the positioning of nuclei, and possibly other organelles, within the cytoplasm. The experimental evidence suggests that nesprins also occur at the inner nuclear membrane, where they interact with the nuclear lamina. In this paper, we consider whether this is consistent with current ideas about nesprin anchorage and about mechanisms for nuclear import of membrane proteins. Nesprins are a family of spectrin repeat proteins The function of short nesprin forms that lack an actinbinding domain is unclear, although most of them do contain the sequences required for direct interaction with emerin and lamin A/C in the nucleoplasm [1,2,12,13] and a role in linking the INM to the nuclear lamina has been proposed Abbreviations used: CH, calponin homology; EM, electron microscopy; ER, endoplasmic reticulum; INM, inner nuclear membrane; KASH, Klarsicht-ANC-Syne-homology; LINC, linker of nucleoskeleton and cytoskeleton; MEF, mouse embryonic fibroblast; NLS, nuclear localization signal; ONM, outer nuclear membrane. 1 To whom correspondence should be addressed (email [email protected]). 2 Present address: Department of Pathology, Hope Hospital, Salford M6 8HD, U.K. approx. 60 kDa, such as emerin (29 kDa) and nesprin-2-α (49-64 kDa), can enter the nucleus by diffusion through lateral channels of the nuclear pores, without the need for an NLS (nuclear localization signal) sequence Is it possible to reconcile giant nesprins at the INM with current models for INM protein transport? Malik et al

Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery

BACKGROUND: Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified. RESULTS: To search for such proteins twenty three nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells. CONCLUSIONS: The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning