syp-2 : syp-6

SYP-2 interacting protein; "SYP-5 and SYP-6 are novel SC-associated components with distinct SC regulatory properties"

syp-2 : syp-5

SYP-2 interacting protein; "SYP-5 and SYP-6 are novel SC-associated components with distinct SC regulatory properties"

Zhang Z et al. (2020) J Cell Biol "Multivalent weak interactions between assembly units drive synaptonemal complex formation."

Zhou J, Colaiacovo MP, Meng X, Gao J, Zhang F, Liu L, Chen M, Wang R, Zhao L, Zhang Z, Xie S, Liu M, Zhao Q, Nie H, Guo S, Liu Y

[J Cell Biol, 2020]

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.

WBAntibody00002079

Antibody against HDA-1 (Santa Cruz sc-5550). hda-1

Kursel LE et al. (2024) Genetics "The structural role of Skp1 in the synaptonemal complex is conserved in nematodes."

Goktepe K, Kursel LE, Rog O

[Genetics, 2024]

The synaptonemal complex (SC) is a meiotic interface that assembles between parental chromosomes and is essential for gamete formation. While the dimensions and ultrastructure of the SC are conserved across eukaryotes, its protein components are highly divergent. Recently, an unexpected component of the SC has been described in the nematode C. elegans: the Skp1-related proteins SKR-1/2, which are components of the Skp1, Cullin, F-box (SCF) ubiquitin ligase. Here, we find that the role of SKR-1 in the SC is conserved in P. pacificus. The P. pacificus Skp1 ortholog, Ppa-SKR-1, colocalizes with other SC proteins throughout meiotic prophase, where it occupies the middle of the SC. Like in C. elegans, the dimerization interface of Ppa-SKR-1 is required for its SC function. A dimerization mutant, ppa-skr-1F105E, fails to assemble SC and produces almost no progeny. Interestingly, the evolutionary trajectory of SKR-1 contrasts with other SC proteins. Unlike most SC proteins, SKR-1 is highly conserved in nematodes. Our results suggest that the structural role of SKR-1 in the SC has been conserved since the common ancestor of C. elegans and P. pacificus, and that rapidly evolving SC proteins have maintained the ability to interact with SKR-1 for at least 100 million years.

Goldstein P (1982) Worm Breeder's Gazette "chromosomes in C elegans."

Goldstein P

[Worm Breeder's Gazette, 1982]

Only five synaptonemal complexes (SC) (representing the 5 autosomes) are present in wild type him-4 and him-8, ditis hereas there are six SCs (accounting for 5 autosomal bivalents and the XX bivalent) in the C. elegans hermaphrodite. The equivalent X chromosome of the male is present as a heterochromatic 'X-body' in spermatocyte pachytene nuclei. The XX bivalent in wild-type, him-4 and him-8 hermaphrodites (SC#l, 2.5 m in length) represented 6% of the total karyotype length and a SC of this size is missing from the respective male karyotypes. This corresponds with the fact that the total male karyotype length is only approximately 94% that of the hermaphrodite. Associated with the central element of the SC are structures termed 'SC Knobs' that were first described in the wild type hermaphrodite (Goldstein and Slaton, 1982). The six SC knobs present in the wild-type hermaphrodite oocyte pachytene nuclei and the two SC knobs in the male spermatocyte pachytene nuclei are apparently randomly placed with the exception that they are never found at the ends of the SC. This is also true in him-4 and him-8 in which case there are 3 and zero SC knobs in the hermaphrodites, respectively, and one SC knob each in the male pachytene nuclei. The decrease in number of SC knobs in hermaphrodite to male represents a true sex difference. The presence or absence of the SC knobs may influence the X chromosome nondisjunction process and this effect is not localized to the region of the SC on which the SC knob is located.

Gordon, S. et al. (2019) International Worm Meeting "Novel separation-of-function mutants of the synaptonemal complex specifically disrupt alignment of homologous chromosomes during meiotic prophase."

Rog, O., Shea, R., Kursel, L., Xu, K., Gordon, S.

[International Worm Meeting, 2019]

During meiosis, chromosomes pair and align with their homologous partner, and exchange genetic information in a non-conservative manner via crossovers. Both of these processes require a structurally conserved proteinaceous interface called the Synaptonemal Complex (SC) that assembles lengthwise between homologous chromosomes. Despite its ordered appearance in electron micrographs, the SC exhibits liquid-like characteristics that are conserved in yeast, flies and worms. This raised the possibility that liquid-liquid phase-separated SC compartments propagate signals that distribute crossovers and monitor their formation. How does the SC mediate crossover signaling and alignment of homologous chromosomes remains unknown partly because many SC mutants result in complete loss of the SC. We took an evolution-guided approach to subtly perturb specific SC functions. We identified a conserved five amino acid domain in SYP-1 (one of the four SC proteins in C. elegans) and used Deep Mutational Scanning to systematically mutagenize each amino acid in this domain. From this library of mutants, we identified multiple separation-of-function mutations that perturb at least one function of the SC. We will present our progress in characterizing two mutants that support some of the crossover-related functions of the SC but are unable to fully synapse homologous chromosomes. Unlike wildtype SC, which only associates with paired homologous chromosomes aligned along their lengths, these mutants display aberrant SC interactions with paired, unpaired and partially aligned chromosomes. Interestingly, these mutations differentially lessen the tendency of SC subunits to associate with one another. We propose a model that links the ability of SC subunits to self-associate with the SC's ability to enforce alignment of paired chromosomes and to propagate signals inside a liquid-liquid phase-separated compartment.

Goldstein P (1982) Chromosoma "The synaptonemal complexes of Caenorhabditis elegans: pachytene karyotype analysis of male and hermaphrodite wild-type and him mutants."

Goldstein P

[Chromosoma, 1982]

Only five synaptonemal complexes (SC), representing the 5 autosomes, are present in wild-type, him-4 and him-8, Caenorhabditis elegans males, whereas there are six SCs, accounting for 5 autosomal bivalents and the XX bivalent, in the C. elegans hermaphrodite. The univalent X chromosome of the male is present as a heterochromatic 'X- body' in spermatocyte pachytene nuclei. The XX bivalent in wild-type, him-4 and him-8 hermaphrodites (SC1, 2.5 microns in length) represented 6% of the total karyotype length and a SC of this size is missing from the respective male karyotypes. This corresponds with the fact that the total male karyotype length is only approximately 94% that of the hermaphrodite. Associated with the central element of the SC are structures termed 'SC knobs' that were first described in the wild-type hermaphrodite. The six SC knobs present in the wild- type hermaphrodite oocyte pachytene nuclei and the two SC knobs in the male spermatocyte pachytene nuclei are apparently randomly placed with the exception that they are never found at the ends of the SC. This is also true in him-4 and him-8 in which case there are 3 and zero SC knobs in the hermaphrodites, respectively, and one SC knob each in the male pachytene nuclei. The decrease in number of SC knobs in hermaphrodite to male represents a true sex difference. The presence or absence of the SC knobs may influence the X chromosome nondisjunction process and this effect is not localized to the region of the SC on which the SC knob is located.

Picture from Nehrke K et al. (2002) J Biol Chem "The NHX family of Na+-H+ exchangers in Caenorhabditis elegans."

O and P, transgenic nematodes expressing nhx-8::GFP in the lateral seam cells (sc).

Silva N et al. (2014) Dev Cell "The fidelity of synaptonemal complex assembly is regulated by a signaling mechanism that controls early meiotic progression."

Tognetti S, Snijders AP, Encheva V, Ferrandiz N, Lightfoot J, Martinez-Perez E, Hanni S, Faull P, Furger A, Silva N, Speck C, Telecan O, Barroso C

[Dev Cell, 2014]

Proper chromosome segregation during meiosis requires the assembly of the synaptonemal complex (SC) between homologous chromosomes. However, the SC structure itself is indifferent to homology, and poorly understood mechanisms that depend on conserved HORMA-domain proteins prevent ectopic SC assembly. Although HORMA-domain proteins are thought to regulate SC assembly as intrinsic components of meiotic chromosomes, here we uncover a key role for nuclear soluble HORMA-domain protein HTP-1 in the quality control of SC assembly. We show that a mutant form of HTP-1 impaired in chromosome loading provides functionality of an HTP-1-dependent checkpoint that delays exit from homology search-competent stages until all homolog pairs are linked by the SC. Bypassing of this regulatory mechanism results in premature meiotic progression and licensing of homology-independent SC assembly. These findings identify nuclear soluble HTP-1 as a regulator of early meiotic progression, suggesting parallels with the mode of action of Mad2 in the spindle assembly checkpoint.