SUN/KASH interactions facilitate force transmission across the nuclear envelope

Hongyan Hao,Daniel A Starr

doi:10.1080/19491034.2019.1595313

Abstract

ABSTRACTLINC complexes (Linker of Nucleoskeleton and Cytoskeleton), consisting of inner nuclear membrane SUN (Sad1, UNC-84) proteins and outer nuclear membrane KASH (Klarsicht, ANC-1, and Syne Homology) proteins, are essential for nuclear positioning, cell migration and chromosome dynamics. To test the in vivo functions of conserved interfaces revealed by crystal structures, Cain et al used a combination of Caenorhabditis elegans genetics, imaging in cultured NIH 3T3 fibroblasts, and Molecular Dynamic simulations, to study SUN-KASH interactions. Conserved aromatic residues at the -7 position of the C-termini of KASH proteins and conserved disulfide bonds in LINC complexes play important roles in force transmission across the nuclear envelope. Other properties of LINC complexes, such as the helices preceding the SUN domain, the longer coiled-coils spanning the perinuclear space and higher-order organization may also function to transmit mechanical forces generated by the cytoskeleton across the nuclear envelope.

Highlights

LINC complexes (Linker of Nucleoskeleton and Cytoskeleton), consisting of inner nuclear membrane SUN (Sad1, UNC-84) proteins and outer nuclear membrane KASH (Klarsicht, ANC-1, and Syne Homology) proteins, are essential for nuclear positioning, cell migration and chromosome dynamics
LINC complexes are essential for force transmission across the nuclear envelope Eukaryotes are distinguishable from prokaryotes by the presence of a nuclear envelope separating the genetic material from the cytoplasm
LINC complexes are made of SUN (Sad1, UNC-84) proteins in the inner nuclear membrane and KASH (Klarsicht, ANC-1, and Syne Homology) proteins in the outer nuclear membrane [7]

Summary

Introduction

LINC complexes (Linker of Nucleoskeleton and Cytoskeleton), consisting of inner nuclear membrane SUN (Sad1, UNC-84) proteins and outer nuclear membrane KASH (Klarsicht, ANC-1, and Syne Homology) proteins, are essential for nuclear positioning, cell migration and chromosome dynamics. The crystal structures predict that a number of conserved residues that are likely important for the interaction between SUN and KASH proteins and their ability to transfer mechanical forces across the nuclear envelope (Figure 1b).

Results

Conclusion