Protein-protein interactions in the synaptonemal complex.

Tarsounas, Madalina; Pearlman, Ronald E.; Gasser, Patrick; Park, M S; Møens, Peter B.

doi:10.1091/mbc.8.8.1405

Cited by 51 publications

(60 citation statements)

References 59 publications

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“…Regarding LEs, previous immunogold EM data suggested that SYCP2 is not homogeneously distributed in the LEs, as is the case for SYCP3, but enriched toward the inner edge of the LEs (22,24). However, with the resolution provided by dSTORM, the two proteins SYCP2 and SYCP3 appear to colocalize along the axial LE structures ( Fig.…”

Section: Resultsmentioning

confidence: 75%

Elucidation of synaptonemal complex organization by super-resolution imaging with isotropic resolution

Schücker¹,

Holm

Franke

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

130

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Synaptonemal complexes (SCs) are meiosis-specific multiprotein complexes that are essential for synapsis, recombination, and segregation of homologous chromosomes, but the molecular organization of SCs remains unclear. We used immunofluorescence labeling in combination with super-resolution imaging and average position determination to investigate the molecular architecture of SCs. Combination of 2D super-resolution images recorded from different areas of the helical ladder-like structure allowed us to reconstruct the 3D molecular organization of the mammalian SC with isotropic resolution. The central element is composed of two parallel cables at a distance of ∼100 nm, which are oriented perpendicular to two parallel cables of the lateral element arranged at a distance of ∼220 nm. The two parallel cable elements form twisted helical structures that are connected by transversal filaments by their N and C termini. A single-cell preparation generates sufficient localizations to compile a 3D model of the SC with nanometer precision.super-resolution imaging | synaptonemal complex | dSTORM | meiosis | average position determination T he synaptonemal complex (SC) is a well-preserved meiosisspecific protein complex among different species (1, 2). As revealed by transmission electron microscopy (TEM), when fully assembled, SCs are 200-nm-wide, ribbon-like structures that extend all along a chromosome bivalent (3, 4). SCs have a characteristic ladder-like organization that is highly conserved through evolution and consists of two lateral elements (LEs), at which chromatin of homologous chromosomes is attached, and a central region (CR). The CR holds the homologous chromosomes together and is made up of numerous transversal filaments (TFs) and the central element (CE).At present, seven protein components of the synaptonemal complex have been identified in mammals, namely, the LE proteins SYCP2 and SYCP3 (5, 6); the TF protein SYCP1 (7); and the CE-specific proteins SYCE1, SYCE2, SYCE3, and TEX12 (8-10) (Figs. S1 and S2). However, in addition to the identification of SC protein components and the investigation of interaction partners, the establishment of a model of the molecular architecture remains indispensable for the understanding of its function and assembly process. Due to the resolution limit of conventional fluorescence microscopy, information about the molecular organization of SCs has been mainly obtained by immunogold EM (11). In standard immunogold EM preparations, gold particles are localized with nanometer resolution and the localization precision is mainly limited by the size of the primary and secondary IgG antibodies and the gold signal density (12-14). However, sample preparation is time-consuming and quantitative analysis of the signal is tedious because of the low binding efficiency of goldlabeled antibodies. Because the structural resolution is also determined by the labeling density (15), immunogold EM cannot visualize the different SC proteins as continuous structures. Therefore, the construction of ...

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Section: Resultsmentioning

confidence: 75%

Elucidation of synaptonemal complex organization by super-resolution imaging with isotropic resolution

Schücker¹,

Holm

Franke

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

130

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“…We found that yeast Red1 is SUMOylated during early meiosis concomitantly with the appearance of SCs. Interestingly, when we looked in human 293T cells that express tagged versions of either SUMO1 or SUMO2 (humans possess three SUMO variants), we found that Sycp3 (alias Scp3, Cor1), a possible functional analogue of yeast Red1 (39), which is known to bind human Ubc9 (40), is modified specifically by SUMO2 (Fig. S7).…”

Section: Discussionmentioning

confidence: 99%

Synaptonemal complex formation and meiotic checkpoint signaling are linked to the lateral element protein Red1

Eichinger

Jentsch

2010

Proc. Natl. Acad. Sci. U.S.A.

100

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Meiosis generates four haploid daughters from a diploid parental cell. Central steps of meiosis are the pairing and recombination of homologous chromosomes followed by their segregation in two rounds of cell division. Meiotic recombination is monitored by a specialized DNA damage checkpoint pathway and is guided by a unique chromosomal structure called synaptonemal complex (SC), but how these events are coordinated is unclear. Here, we identify the SC protein Red1 as a crucial regulator of early meiosis. Red1 interacts with two subunits of the 9-1-1 checkpoint complex via two distinct 9-1-1 subunit-specific motifs. Association of 9-1-1 with Red1 is essential not only for meiotic checkpoint activation but for SC formation. Moreover, Red1 becomes SUMO-modified, which fosters interaction of Red1 with the central SC element Zip1, thereby securing timely SC formation. Thus, Red1, in addition to its structural role in the SC, is a crucial coordinator of meiosis by coupling checkpoint signaling to SC formation.checkpoint | meiosis | SUMO T he central activity of meiosis is the equal distribution of the genetic material of a diploid cell into four daughter cells. A key step of meiosis occurs in pachytene, in which the homologous chromosomes (i.e., the parental chromosomes, each containing two sister chromatids) align (synapsis). This alignment facilitates the exchange of parental information by homologous recombination and is crucial for chromosome segregation during the first meiotic division.The juxtaposition of the homologs in pachytene involves a unique chromosome structure known as the synaptonemal complex (SC), which assembles along the entire length of the bundled chromosomes (1, 2). The SC-induced arrangement of chromosomes appears to favor genetic exchange between homologs rather than sister chromatids. SC formation starts along each pair of homologous sister chromatids with the assembly of 50-nm-thick fibers, termed axial elements, which later become the so-called "lateral elements" of the SC. The axial elementcoated parental homologs finally associate via components of the central element, which zip the axial elements together, forming the SC. In Saccharomyces cerevisiae, the proteins Hop1 and Red1 are structural components of the lateral element, whereas the coiled-coil protein Zip1, which homo (oligo)-dimerizes during SC formation, forms the "steps" of the ladder-like central region. SC "zipping" is thought to take place by serial Zip1-Red1 interactions along the entire SC axis (1, 2).Early meiosis is under the control of the meiotic recombination checkpoint (called the meiotic checkpoint here; it is also known as the pachytene checkpoint), which prevents meiotic progression in the presence of unrepaired recombination intermediates. A key element of the meiotic surveillance pathway is the ring-shaped, heterotrimeric 9-1-1 complex (the proteins Rad9, Hus1, and Rad1 in mammals; the proteins Ddc1, Mec3, and Rad17 in S. cerevisiae), which is structurally related to the homotrimeric DNA-encircling DNA polymerase...

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“…Both proteins are meiosis-specific and are predicted to contain extensive coiled coil domains in their C termini (34,35). Furthermore, the C termini of both proteins mediate homodimerization in the two-hybrid system (10,36). SPC3 has been shown to be phosphorylated and, furthermore, that the pattern of phosphorylation is dynamic throughout meiotic prophase (37).…”

Section: Discussionmentioning

confidence: 99%

Red1p, a MEK1-dependent Phosphoprotein That Physically Interacts with Hop1p during Meiosis in Yeast

Santos

Hollingsworth

1999

Journal of Biological Chemistry

116

138

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The synaptonemal complex (SC) is a proteinaceous structure formed between pairs of homologous chromosomes during prophase I of meiosis. The proper assembly of axial elements (AEs), lateral components of the SC, during meiosis in the yeast, Saccharomyces cerevisiae, is essential for wild-type levels of recombination and for the accurate segregation of chromosomes at the first meiotic division. Genetic experiments have indicated that the stoichiometry between two meiosis-specific components of AEs in S. cerevisiae, HOP1 and RED1, is critical for proper assembly and function of the SC. A third meiosis-specific gene, MEK1, which encodes a putative serine/threonine protein kinase, is also important for proper AE function, suggesting that AE formation is regulated by phosphorylation. In this paper, we demonstrate that Mek1p is a functional kinase in vitro and that catalytic activity is an essential part of the meiotic function of Mek1 in vivo. Immunoblot analysis revealed that Red1p is a MEK1-dependent phosphoprotein. Co-immunoprecipitation experiments demonstrated that the interaction between Hop1p and Red1p is enhanced by the presence of MEK1. Thus, MEK1-dependent phosphorylation of Red1p facilitates the formation of Hop1p/Red1p hetero-oligomers, thereby enabling the formation of functional AEs.

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Protein-protein interactions in the synaptonemal complex.

Cited by 51 publications

References 59 publications

Elucidation of synaptonemal complex organization by super-resolution imaging with isotropic resolution

Elucidation of synaptonemal complex organization by super-resolution imaging with isotropic resolution

Synaptonemal complex formation and meiotic checkpoint signaling are linked to the lateral element protein Red1

Red1p, a MEK1-dependent Phosphoprotein That Physically Interacts with Hop1p during Meiosis in Yeast

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