Linker of nucleoskeleton and cytoskeleton complex proteins in cardiomyopathy

Matthew J Stroud

doi:10.1007/s12551-018-0431-6

Abstract

The linker of nucleoskeleton and cytoskeleton (LINC) complex couples the nuclear lamina to the cytoskeleton. The LINC complex and its associated proteins play diverse roles in cells, ranging from genome organization, nuclear morphology, gene expression, to mechanical stability. The importance of a functional LINC complex is highlighted by the large number of mutations in genes encoding LINC complex proteins that lead to skeletal and cardiac myopathies. In this review, the structure, function, and interactions between components of the LINC complex will be described. Mutations that are known to cause cardiomyopathy in patients will be discussed alongside their respective mouse models. Furthermore, future challenges for the field and emerging technologies to investigate LINC complex function will be discussed.

Highlights

The nuclear envelope (NE) plays a critical role in dividing the cytoplasm from the nucleus
The NE is comprised of the inner nuclear membrane (INM) and the outer nuclear membrane (ONM), which is contiguous with the endoplasmic reticulum (Fig. 1)
These membranes are separated by the perinuclear space (PNS) and are periodically joined by nuclear pore complexes (NPC) that allow bidirectional transport of macromolecules across the NE (Brohawn et al 2009; Gorlich and Kutay 1999; Grossman et al 2012)

Summary

Introduction

The nuclear envelope (NE) plays a critical role in dividing the cytoplasm from the nucleus. Both Nesprin 3 isoforms contain a C-terminal KASH domain that binds SUN 1/2 and localizes Nesprin 3 to the nuclear envelope in cardiac tissue (Ketema et al 2013).

Results

Conclusion