Mps2 links Csm4 and Mps3 to form a telomere-associated LINC complex in budding yeast

Abstract

The linker of the nucleoskeleton and cytoskeleton (LINC) complex is composed of two transmembrane proteins: the KASH domain protein localized to the outer nuclear membrane and the SUN domain protein to the inner nuclear membrane. In budding yeast, the sole SUN domain protein, Mps3, is thought to pair with either Csm4 or Mps2, two KASH-like proteins, to form two separate LINC complexes. Here, we show that Mps2 mediates the interaction between Csm4 and Mps3 to form a heterotrimeric telomere-associated LINC (t-LINC) complex in budding yeast meiosis. Mps2 binds to Csm4 and Mps3, and all three are localized to the telomere. Telomeric localization of Csm4 depends on both Mps2 and Mps3; in contrast, Mps2’s localization depends on Mps3 but not Csm4. Mps2-mediated t-LINC complex regulates telomere movement and meiotic recombination. By ectopically expressing CSM4 in vegetative yeast cells, we reconstitute the heterotrimeric t-LINC complex and demonstrate its ability to tether telomeres. Our findings therefore reveal the heterotrimeric composition of the t-LINC complex in budding yeast and have implications for understanding variant LINC complex formation.

High Temporal Resolution 3D Live-Cell Imaging of Budding Yeast Meiosis Defines Discontinuous Actin/Telomere-Mediated Chromosome Motion, Correlated Nuclear Envelope Deformation and Actin Filament Dynamics

“…How do the molecular ensembles that undergo Myo2/actin-mediated motion manage to assemble? Several lines of evidence point to concerted assembly of telomere/Ndj1– LINC—Myo2—actin complexes ( Conrad et al, 2007 , 2008 ; Scherthan et al, 2007 ; Kosaka et al, 2008 ; Wanat et al, 2008 ; Lee et al, 2012 , 2020 ; Fan et al, 2020 ). Furthermore, it would be sensible if such complexes only assembled when the possibility of actin-mediated motion exists.…”

“…Five molecules other than actin have also been implicated in actin-mediated motion ( Fan et al, 2020 ; Lee et al, 2020 ). Ndj1 is a meiosis-specific protein that connects the telomere to the LINC complex via Mps3, a SUN domain protein that spans the nuclear membrane.…”

“…Mps2 and Csm4 are related coiled coil proteins that interact with one another and mediate linkage of Mps3 to myosin Myo2 which, in turn, interacts with actin. Mutations that delete or alter any one of the involved proteins causes a severe reduction of rapid chromosome movement at mid-meiotic prophase and a delay in homolog pairing ( Conrad et al, 2007 , 2008 ; Scherthan et al, 2007 ; Kosaka et al, 2008 ; Wanat et al, 2008 ; Lee et al, 2012 , 2020 ; Fan et al, 2020 ). Importantly, in mitotically dividing yeast cells, Myo2 mediates the transport of several different types of cargos along actin fibers (e.g., Beach et al, 2000 ; Schott et al, 2002 ).…”

Homologous chromosome pairing: The linchpin of accurate segregation in meiosis

“…Csm4 and Mps2 are KASH-like proteins, with Csm4 expression being meiosis-specific. Both paralogs mediate rapid chromosome motility by interacting with myosin II, which travels along actin filaments (Fan et al, 2020;Lee et al, 2020;Wanat et al, 2008). Loss of Ndj1, Mps3 or Csm4 compromises telomere clustering and HR during meiosis (Chua & Roeder, 1997;Conrad et al, 1997Conrad et al, , 2007Wanat et al, 2008).…”

A cooperative network at the nuclear envelope counteracts LINC-mediated forces during oogenesis in C. elegans

“…During meiosis, homologous chromosomes must pair, synapse, and undergo controlled DNA double-strand breaks (DSBs) and repair (1,2). Oocyte nuclei are subjected to mechanical forces generated by the cytoskeleton and transmitted to the nuclear envelope (NE) through linker of nucleoskeleton and cytoskeleton (LINC) complexes (3)(4)(5)(6)(7)(8)(9)(10)(11). These forces are important for meiotic chromosome dynamics, nuclear positioning, and migration of maturing oocytes in the germ line (12,13).…”