Meiotic cohesin subunits RAD21L and REC8 are positioned at distinct regions between lateral elements and transverse filaments in the synaptonemal complex of mouse spermatocytes

Abstract

Cohesins containing a meiosis-specific α-kleisin subunit, RAD21L or REC8, play roles in diverse aspects of meiotic chromosome dynamics including formation of axial elements (AEs), assembly of the synaptonemal complex (SC), recombination of homologous chromosomes (homologs), and cohesion of sister chromatids. However, the exact functions of individual α-kleisins remain to be elucidated. Here, we examined the localization of RAD21L and REC8 within the SC by super-resolution microscopy, 3D-SIM. We found that both RAD21L and REC8 were localized at the connection sites between lateral elements (LEs) and transverse filaments (TFs) of pachynema with RAD21L locating interior to REC8 sites. RAD21L and REC8 were not symmetrical in terms of synaptic homologs, suggesting that the arrangement of different cohesins is not strictly fixed along all chromosome axes. Intriguingly, some RAD21L signals, but not REC8 signals, were observed between unsynapsed regions of AEs of zygonema as if they formed a bridge between homologs. Furthermore, the signals of recombination intermediates overlapped with those of RAD21L to a greater degree than with those of REC8. These results highlight the different properties of two meiotic α-kleisins, and strongly support the previous proposition that RAD21L is an atypical cohesin that establishes the association between homologs rather than sister chromatids.

Superresolution microscopy reveals the three-dimensional organization of meiotic chromosome axes in intact Caenorhabditis elegans tissue

“…However, these proteins do not completely disappear from synapsed axes and may therefore provide a persistent bridge between cohesins and the SC central region even when their abundance is reduced. Consistent with this idea, cohesin complexes and proteins of the central region were found to be separated by about 20 nm in mouse spermatocytes (24), suggesting the presence of other components between the central region proteins and cohesin complexes.…”

“…This observation indicates that the electron-dense elements that flank the SC may not correspond to assemblies of axis proteins, although some axis proteins appear to localize at or near these structures (22). Although recent work has illuminated some structural details of axis proteins and their interactions (16,(22)(23)(24), the overall organization of the chromosome axis remains largely undetermined.…”

Super-resolution microscopy reveals the three-dimensional organization of meiotic chromosome axes in intactC. eleganstissue

“…However, these proteins do not completely disappear from synapsed axes, and may therefore provide a persistent bridge between cohesins and the SC central region also in other organisms. Consistent with this idea, cohesin complexes and proteins of the central region were found to be separated by about 20 nm in mouse spermatocytes (28) suggesting that HORMA-domain proteins might indeed form a conserved interface between central region proteins and cohesin complexes.…”

“…This indicates that the electron-dense elements that flank the SC may not correspond to assemblies of axis proteins, although some axis proteins appear to localize near these structures (26). Recent work has illuminated some structural details of axis proteins and their interactions (13,(26)(27)(28). However, the overall organization of the chromosome axis remains largely undetermined.…”

A conserved mechanism for meiotic chromosome organization through self-assembly of a filamentous chromosome axis core

“…Significant questions remain regarding how the SC lateral elements and transverse filaments might interact, and the role of cohesin complexes in this interaction is also unknown. Recently, it was reported that REC8 and RAD21L, meiosis-specific cohesin complex kleisin subunits, both localize slightly "inside" SYCP3; that is, they are situated closer to the SYCP1 transverse filaments than the SYCP2:SYCP3 complex (90). These data suggest that cohesin complexes may somehow be integrated into the structure of the SC, in a manner that is not yet well-understood.…”