Multivalent weak interactions between assembly units drive synaptonemal complex formation

Abstract

The synaptonemal complex (SC) is an ordered but highly dynamic structure assembled between homologous chromosomes to control interhomologous crossover formation, ensuring accurate meiotic chromosome segregation. However, the mechanisms regulating SC assembly and dynamics remain unclear. Here, we identified two new SC components, SYP-5 and SYP-6, in Caenorhabditis elegans that have distinct expression patterns and form distinct SC assembly units with other SYPs through stable interactions. SYP-5 and SYP-6 exhibit diverse in vivo SC regulatory functions and distinct phase separation properties in cells. Charge-interacting elements (CIEs) are enriched in SC intrinsically disordered regions (IDRs), and IDR deletion or CIE removal confirmed a requirement for these elements in SC regulation. Our data support the theory that multivalent weak interactions between the SC units drive SC formation and that CIEs confer multivalency to the assembly units.

Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis

“…The nature and location of the syp-1 K42E mutation -a charge-altering substitution outside the predicted coiledcoil -argues that hydrophobic interactions or the predicted coiled-coils are not solely responsible for phase separation. In contrast, syp-1 K42E alters an existing CIE, supporting a role for CIEs in driving phase separation of the SC [12,45]. Future biochemical characterization of protein-protein interactions in wildtype and mutant SC are likely to illuminate the molecular interactions that underlie SC organization.…”

“…Stacking of SC subunits is likely to underlie phase separation, which can be driven by weak multivalent interactions [44]. For the SC, several non-mutually exclusive mechanisms have been proposed: weak hydrophobic interactions [18], interactions between the predicted coiled-coils, and interactions between charge-interacting elements (CIEs) [12]. The nature and location of the syp-1 K42E mutation -a charge-altering substitution outside the predicted coiledcoil -argues that hydrophobic interactions or the predicted coiled-coils are not solely responsible for phase separation.…”

“…The SC is composed of a handful of subunits (six in C. elegans [7][8][9][10][11][12]) that occupy stereotypic locations relative to the axes ( Fig. 1A; [12][13][14][15][16]). However, we have limited understanding of how SC proteins interact with one another, or how their structure helps them to carry out functions such as aligning the homologs or regulating crossovers.…”

“…Genetic analyses in multiple model systems, however, have shown that the width of the SC is determined, at least in part, by the length of predicted coiled-coils in SC subunits referred to as transverse filament proteins [20][21][22], and that the C-termini of these proteins are required for axis associations [23,24]. In worms these transverse filament proteins include SYP-1 and SYP-5/6, which span, in a head-to-head orientation, the ~100 nm between the axes [7,12,16]. The contributions of other domains to specific functions or structural features are much less clear.…”

Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase inC. elegans

“…This suggests that recruitment or activation of one or more kinases that phosphorylate HIM-3 is dependent on SYP proteins. The enrichment of SC central proteins on short arms in late pachytene [4,[38][39][40][41] , coincident in location and timing with phosphorylated HIM-3 partitioning, further suggests the central element provides a platform for a kinase to phosphorylate HIM-3 preferentially on short arms upon crossover designation.…”