Department of Cell Biology, Erasmus Medical Center, 3000 CA Rotterdam, Netherlands.
J Cell Biol. 2011 Jun 13;193(6):1083-99. doi: 10.1083/jcb.201012179. Epub 2011 Jun 6.
The ends of growing microtubules (MTs) accumulate a set of diverse factors known as MT plus end-tracking proteins (+TIPs), which control microtubule dynamics and organization. In this paper, we identify SLAIN2 as a key component of +TIP interaction networks. We showed that the C-terminal part of SLAIN2 bound to end-binding proteins (EBs), cytoplasmic linker proteins (CLIPs), and CLIP-associated proteins and characterized in detail the interaction of SLAIN2 with EB1 and CLIP-170. Furthermore, we found that the N-terminal part of SLAIN2 interacted with ch-TOG, the mammalian homologue of the MT polymerase XMAP215. Through its multiple interactions, SLAIN2 enhanced ch-TOG accumulation at MT plus ends and, as a consequence, strongly stimulated processive MT polymerization in interphase cells. Depletion or disruption of the SLAIN2-ch-TOG complex led to disorganization of the radial MT array. During mitosis, SLAIN2 became highly phosphorylated, and its interaction with EBs and ch-TOG was inhibited. Our study provides new insights into the molecular mechanisms underlying cell cycle-specific regulation of MT polymerization and the organization of the MT network.
生长中的微管（MTs）的末端会积累一组称为 MT 加端追踪蛋白（+TIPs）的多种因子，这些因子控制着微管的动态和组织。在本文中，我们确定 SLAIN2 为 +TIP 相互作用网络的关键组成部分。我们表明，SLAIN2 的 C 端部分与末端结合蛋白（EBs）、细胞质连接蛋白（CLIPs）和 CLIP 相关蛋白结合，并详细描述了 SLAIN2 与 EB1 和 CLIP-170 的相互作用。此外，我们发现 SLAIN2 的 N 端与 ch-TOG 相互作用，ch-TOG 是 MT 聚合酶 XMAP215 的哺乳动物同源物。通过其多种相互作用，SLAIN2 增强了 ch-TOG 在 MT 加端的积累，从而强烈刺激了间期中的连续 MT 聚合。SLAIN2 的耗竭或破坏导致放射状 MT 阵列的紊乱。在有丝分裂期间，SLAIN2 高度磷酸化，其与 EBs 和 ch-TOG 的相互作用受到抑制。我们的研究为细胞周期特异性调节 MT 聚合和 MT 网络组织的分子机制提供了新的见解。
