Differential incorporation of SUN-domain proteins into LINC complexes is coupled to gene expression

Christopher K May,Christopher W Carroll,Qiang Wang

doi:10.1371/journal.pone.0197621

Christopher K May, Christopher W Carroll + Show 1 more

Open Access

https://doi.org/10.1371/journal.pone.0197621

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Journal: PloS one	Publication Date: May 29, 2018
Citations: 21	License type: CC BY 4.0

Affiliation: Yale University

Abstract

LInkers of Nucleoskeleton and Cytoskeleton (LINC) complexes, composed of SUN and KASH-domain proteins, span the nuclear envelope and physically connect the nuclear interior to cytoskeletal elements. Most human cells contain two SUN proteins, Sun1 and Sun2, and several KASH-proteins suggesting that multiple functionally distinct LINC complexes co-exist in the nuclear envelope. We show here, however, that while Sun1 and Sun2 in HeLa cells are each able to bind KASH-domains, Sun1 is more efficiently incorporated into LINC complexes under normal growth conditions. Furthermore, the balance of Sun1 and Sun2 incorporated into LINC complexes is cell type-specific and is correlated with SRF/Mkl1-dependent gene expression. In addition, we found that Sun1 has a LINC complex-independent role in transcriptional control, possibly by regulating the SRF/Mkl1 pathway. Together, these data reveal novel insights into the mechanisms of LINC complex regulation and demonstrate that Sun1 modulates gene expression independently of its incorporation into LINC complexes.

Highlights

A defining feature of eukaryotic cells is the compartmentalization of the genome into a membrane-enclosed nucleus
Sun1 is more efficiently incorporated into LInkers of Nucleoskeleton and Cytoskeleton (LINC) complexes than Sun2
In order to demonstrate the specificity of the nesprin antibodies, we expressed GFP-SR-KASH, which contains the KASH-domain, transmembrane segment, and membrane-proximal cytoplasmic sequences derived from Nesprin2

Summary

Introduction

A defining feature of eukaryotic cells is the compartmentalization of the genome into a membrane-enclosed nucleus. These data suggest that Sun1 inhibits signaling through LINC complex-independent inhibition of Mkl1/SRF gene expression in the nucleus. Consistent with previous reports demonstrating that GFP-SR-KASH efficiently blocks LINC complex assembly by outcompeting endogenous Nesprin proteins for SUN-domain binding, GFP-SR-KASH expression inhibited the co-precipitation of Sun1 with Nesprin1 (Fig 1A) [30, 31].

Results

Conclusion