A conserved KASH domain protein associates with telomeres, SUN1, and dynactin during mammalian meiosis

Abstract

n yeasts and worms, KASH (Klarsicht/ANC-1/Syne/ homology) domain and SUN (Sad-1/UNC-84) domain nuclear envelope (NE) proteins play a crucial role in meiotic chromosome movement and homologue pair-ing. However, although the vertebrate SUN domain pro-tein SUN1 is involved in these processes, its partner has remained identified. Based on subcellular localiza-tion screening in mouse spermatocytes, we identified a novel germ cell-specific protein, KASH5, that localized exclusively at telomeres from the leptotene to diplotene stages in both spermatocytes and oocytes. KASH5 pos-sesses hitherto unknown KASH-related sequences that directly interacted with SUN1 and mediated telomere loca-lization. Thus, KASH5 is a mammalian meiosis-specific KASH domain protein. We show that meiotic chromo-some movement depended on microtubules and that KASH5 interacted with the microtubule-associated dynein-dynactin complex. These results suggest that KASH5 connects the telomere-associated SUN1 protein to the cytoplasmic force-generating mechanism involved in meiotic chromosome movement. Our study strongly sug-gests that the meiotic homologue-pairing mechanism mediated by the SUN-KASH NE bridge is highly con-served among eukaryotes. © 2012 Morimoto et al.