The nuclear envelope (NE) undergoes dynamic remodeling to maintain NE integrity, a process involving the inner nuclear membrane protein LEM2 recruiting CHMP7/Cmp7 and then ESCRT-III. However, prior work has hinted at CHMP7/ESCRT-independent mechanisms. To identify such mechanisms, we studied NE assembly in Schizosaccharomyces japonicus, a fission yeast that undergoes partial mitotic NE breakdown and reassembly. S. japonicus cells lacking Cmp7 have compromised NE sealing after mitosis but are viable. A genetic screen identified mutations that promote NE integrity in cmp7Δ cells. Unexpectedly, loss of Lem2 or its interacting partner Nur1 suppressed cmp7Δ defects. In the absence of Cmp7, Lem2 formed aggregates that appear to interfere with ESCRT-independent NE sealing. A gain-of-function mutation implicated a membrane and ESCRT-III regulator, Alx1, in this alternate pathway. Additional results suggest a potentially general role for unsaturated fatty acids in NE integrity. These findings establish the existence of mechanisms for NE sealing independent of the canonical ESCRT pathway.

中文翻译：

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独立于经典 ESRT 途径的促进核膜组装的因素

核膜 (NE) 经历动态重塑以维持 NE 完整性，该过程涉及内核膜蛋白 LEM2 募集 CHMP7/Cmp7，然后募集 ESCRT-III。然而，先前的工作已经暗示了 CHMP7/ESCRT 独立机制。为了确定这种机制，我们研究了日本裂殖酵母（Schizosaccharomyces japonicus）中的 NE 组装，这是一种经历部分有丝分裂 NE 分解和重新组装的裂殖酵母。缺乏 Cmp7 的日本参细胞在有丝分裂后会损害 NE 封闭，但仍能存活。基因筛选发现了促进 cmp7Δ 细胞 NE 完整性的突变。出乎意料的是，Lem2 或其相互作用伙伴 Nur1 的缺失抑制了 cmp7Δ 缺陷。在没有 Cmp7 的情况下，Lem2 形成的聚集体似乎干扰了不依赖于 ESCRT 的 NE 密封。功能获得性突变表明该替代途径中存在膜和 ESCRT-III 调节因子 Alx1。其他结果表明不饱和脂肪酸在 NE 完整性中具有潜在的普遍作用。这些发现证实了独立于经典 ESRT 通路的 NE 封闭机制的存在。