NUCLEAR STRUCTURE AND DYNAMICS

Regular sperm head formation implicitly depends on a quite extensive but well-directed nuclear remodelling that involves nuclear movement, compaction, polarization and reshaping form round to elongate. To date, the mechanisms how nuclei shape to form a functional sperm head are unknown. Recent studies have identified novel nuclear envelope bridging complexes, referred to as LINC complexes (linker of nucleoskeleton and cytoskeleton), that mediate a direct connection of nuclear structures with the cytoskeleton. LINC complexes are pivotal for nuclear migration, positioning and anchoring and for meiotic chromosome movements. Furthermore, they were shown to be essential for maintaining nuclear morphology and shape. Therefore, we propose that they could hold a key role in sperm head formation as well. Consistently, we found that nuclear elongation and reshaping closely correlates with formation and a conspicuous opposite polarization of two novel spermiogenesis-specific LINC complexes. Furthermore, we recently could identify Sun4 as key player in sperm-specific nuclear shaping. The aim of the current project is to further enlighten our still fragmentary knowledge about formation and composition of LINC complexes in spermatids and to determine the actual relevance of LINC complexes and their components for nuclear remodelling, shaping and fertility.

Germ cells are specialized cells which are of vital importance for eukaryotic life. They are the lynchpin of sexual reproduction and provide the enduring link between generations. Germ cells are designated to generate haploid cells that are committed to join with other gametes to create a new diploid organism. Therefore, during meiotic division cells have to recognize and unambiguously segregate the homologous chromosomes to reduce the genome.

It turned out that during meiotic prophase I the NE functions as a platform for the highly coordinated chromosomal movements which in turn are essential for pairing and recombination of the homologs. On entry into meiosis chromosomal ends firmly attach to nuclear envelope and start to move to congregate at one pole of the nucleus. Thereby chromosomes are trailed into close vicinity, a process that is supposed to further interhomolog interactions. Meiotic telomere attachment and their directed movements on the plane of the NE depend on a general reorganization of the NE. On the one hand, it concerns most central components of the inner nuclear membrane, which provide docking sites for telomeres. Attachment and movement of meiotic telomeres is mediated by the so-called LINC-complexes, which represent most central NE bridges that are used to transfer forces from the cytoplasm to the nucleus and, even more, across the NE to the nuclear interior.

At least in mammals, movement of telomeres within the NE requires a more general reorganization of the NE and in particular of the nuclear lamina. Mammalian meiotic cells lack three of the typically four somatic lamin isoforms, but instead express a unique short lamin, which is called lamin C2. We could show that this lamin, which can be considered as a kind of a “natural lamin deletion mutant”, holds a key function in chromosomal pairing and recombination and thus represents an essential determinant for fertility.

Meiosis is highly conserved in eukaryotic evolution. EM studies demonstrated the presence of synaptonemal complex (SC) like structures in fungi, plants and animals. However, the as yet identified proteins forming these structures in the different clades appear not to be genetically related. Even between the commonly used animal model organisms C. elegans, Drosophila and the mouse the main protein components of the SCs - even though they to some degree show structural similarity - seem to be not conserved on the amino acid level. This led to the conclusion that synaptonemal complexes may have evolved repeatedly during evolution.

Analyzing this issue in more detail, we in the past years could actually find that mammalian SC proteins are evolutionary highly related to that of basal metazoan organisms such as cnidarians and sponges. Thus, our results demonstrated that at least in metazoans the SC has a common origin, which includes the basic structural components as well as regulatory SC elements.