Structural insights into LINC complexes

•SUN-proteins and KASH-proteins form mechanical connections across the nuclear envelope.•Crystal structures reveal that these LINC complexes are built from SUN trimers interacting with three KASH peptides.•LINC complexes might define the spacing of inner and outer nuclear membrane.•LINC complexes are involved in a growing number of diverse biological functions.

Communication between nucleus and cytoplasm extends past molecular exchange and critically includes mechanical wiring. Cytoskeleton and nucleoskeleton are connected via molecular tethers that span the nuclear envelope. Sad1, UNC84 (SUN)-domain proteins spanning the inner nuclear membrane and Klarsicht, ANC-1 and SYNE/Nesprin-1 and -2 Homology (KASH)-peptide bearing proteins residing in the outer nuclear membrane directly bind and constitute the core of the LInkers of Nucleoskeleton and Cytoskeleton (LINC) complex. These connections appear critical for a growing number of biological processes and aberrations are implicated in a host of diverse diseases, including muscular dystrophies, cardiomyopathies, and premature aging. We discuss recent developments in this vibrant research area, particularly in context of first structural insights into LINC complexes reported in the past year.