Department of Chemistry, Shizuoka University, Suruga-ku, Shizuoka 422-8529, Japan.
J Cell Biol. 2013 Feb 18;200(4):385-95. doi: 10.1083/jcb.201207168. Epub 2013 Feb 11.
During meiosis, telomeres cluster and promote homologous chromosome pairing. Telomere clustering requires the interaction of telomeres with the nuclear membrane proteins SUN (Sad1/UNC-84) and KASH (Klarsicht/ANC-1/Syne homology). The mechanism by which telomeres gather remains elusive. In this paper, we show that telomere clustering in fission yeast depends on microtubules and the microtubule motors, cytoplasmic dynein, and kinesins. Furthermore, the γ-tubulin complex (γ-TuC) is recruited to SUN- and KASH-localized telomeres to form a novel microtubule-organizing center that we termed the "telocentrosome." Telocentrosome formation depends on the γ-TuC regulator Mto1 and on the KASH protein Kms1, and depletion of either Mto1 or Kms1 caused severe telomere clustering defects. In addition, the dynein light chain (DLC) contributes to telocentrosome formation, and simultaneous depletion of DLC and dynein also caused severe clustering defects. Thus, the telocentrosome is essential for telomere clustering. We propose that telomere-localized SUN and KASH induce telocentrosome formation and that subsequent microtubule motor-dependent aggregation of telocentrosomes via the telocentrosome-nucleated microtubules causes telomere clustering.
在减数分裂过程中，端粒簇集并促进同源染色体配对。端粒簇集需要端粒与核膜蛋白 SUN（Sad1/UNC-84）和 KASH（Klarsicht/ANC-1/Syne homology）相互作用。端粒聚集的机制仍不清楚。在本文中，我们表明，裂殖酵母中端粒的簇集依赖于微管和微管马达，细胞质动力蛋白和驱动蛋白。此外，γ-微管蛋白复合物（γ-TuC）被招募到 SUN 和 KASH 定位的端粒上，形成一个新的微管组织中心，我们称之为“端中心体”。端中心体的形成依赖于γ-TuC 调节剂 Mto1 和 KASH 蛋白 Kms1，Mto1 或 Kms1 的耗竭导致严重的端粒簇集缺陷。此外，动力蛋白轻链（DLC）有助于端中心体的形成，同时耗尽 DLC 和动力蛋白也会导致严重的簇集缺陷。因此，端中心体对于端粒的簇集是必不可少的。我们提出，端粒定位的 SUN 和 KASH 诱导端中心体的形成，随后通过端中心体核微管依赖性的端中心体聚集导致端粒簇集。
