Horn et al. identify a protein that helps homologous chromosomes pair up in meiosis by connecting them to the microtubule cytoskeleton.
Early in meiosis, chromosomes cluster together so that homologous chromosomes can find each other and pair up to undergo recombination. Clustering is controlled by LINC complexes, which span the nuclear envelope to couple chromosomes to the microtubule-based motor protein cytoplasmic dynein. Dynein can therefore pull chromosomes toward the centrosome on one side of the nucleus.
LINC complexes are formed by members of the SUN and KASH protein families. SUN1 is an inner nuclear membrane protein that, in most organisms, attaches to the telomeres of meiotic chromosomes. A member of the KASH family of outer nuclear membrane proteins links SUN1 to cytoplasmic dynein, but which KASH protein performs this function in mammals is unknown.
Horn et al. focused on KASH5, a recently identified KASH protein expressed in testes and ovaries. KASH5 colocalized with SUN1 at sites where telomeres attached to the nuclear envelope in mouse spermatocytes. Mice lacking KASH5 were infertile. Males, for example, couldn’t produce mature sperm because their spermatocytes arrested early in meiosis after failing to form homologous chromosome pairs. Telomeres were still attached, via SUN1, to the nuclear envelope, but dynein was no longer recruited to these attachment sites, thus abolishing chromosome clustering and homologue pairing.
Having established KASH5 as a member of the meiotic LINC complex in mammals, senior author Brian Burke now wants to identify proteins that connect telomeres to SUN1 at the nuclear periphery.
Text by Ben Short