The missing LINC: a mammalian KASH-domain protein coupling meiotic chromosomes to the cytoskeleton.

Abstract

Pairing of homologous chromosome is a unique event in meiosis that is essential for both haploidization of the genome and genetic recombination. Rapid chromosome movements during meiotic prophase are a key feature of the pairing process. This is usually telomere-led, and in metazoans is dependent upon microtubules and dynein. Chromosome movements culminate in the formation of a meiotic "bouquet" in which nuclear envelope-associated telomeres are clustered at the centrosomal pole of the nucleus. Bouquet formation is thought to facilitate homolog pairing. Recent studies reveal that coupling of telomeres to cytoplasmic dynein is mediated by SUN1 in the inner nuclear membrane (INM) and KASH5 a novel protein of the outer nuclear membrane (ONM). Together SUN1 and KASH5 assemble to form a transluminal LINC (linker of the nucleoskeleton and cytoskeleton) complex that spans both nuclear membranes. SUN1 forms attachment sites for telomeres at the INM while KASH5 functions as a dynein adaptor at the ONM. In mice deficient in KASH5, homologous chromosome pairing does not occur. The result is that meiosis is arrested at the leptotene/zygotene stage of meiotic prophase 1, and as a consequence both male and female mice are infertile. This study demonstrates an essential role for dynein directed telomere movement during meiotic prophase.