Emerin-prelamin A interplay in human fibroblasts
Emerin-prelamin A interplay in human fibroblasts
复制标题
DOI：
10.1042/bc20080175
复制
发表时间：
2009-09-01
影响因子：
2.7
通讯作者：
Lattanzi, Giovanna
中科院分区：
文献类型：
--
作者：
Capanni, Cristina;Del Coco, Rosalba;Lattanzi, Giovanna
背景信息。 Emerin 是一种核膜蛋白，通过与各种核蛋白相互作用，有助于核结构、染色质结构和基因表达。特别是，emerin 在分子上与核纤层相连，核纤层是由核纤层蛋白和内核膜下方的核纤层蛋白结合蛋白组成的蛋白质网络。在核纤层成分中，核纤层蛋白 A 是主要的 emerin 伙伴。核纤层蛋白 A 由 LMNA 基因（核纤层蛋白 A/C 基因）编码，作为前体蛋白（前核纤层蛋白 A）产生，在其 C 末端区域进行转录后修饰，其中 CaaX 基序触发一系列修饰，包括法尼基化、羧甲基化和 ZMPSTE 24（锌金属蛋白酶 Ste24）金属蛋白酶的蛋白水解切割。核纤层蛋白 A 成熟途径受损，导致核纤层蛋白 A 前体积累，与家族性部分脂肪营养不良、MADA（下颌骨发育不良）、维尔纳综合征、哈钦森-吉尔福德早衰综合征和 RD（限制性皮肤病）等罕见疾病的发生有关。结果。在本研究中，我们表明 emerin 和不同的 prelamin A 形式会相互影响彼此的定位。我们发现，人成纤维细胞中非法尼基化以及法尼基化羧甲基化核纤层蛋白 A 前体的积累会改变 emerin 的定位。相反，内核膜处 emerin 的缺失仅导致未加工（非法尼基化）的 prelamin A 异常定位。此外，我们观察到，在无emerin的细胞中，emerin表达的恢复会诱导非法尼基化的prelamin A定位的恢复。结论。这些结果表明 emerin-prelamin A 相互作用影响核组织。这一发现可能与理解核纤层蛋白病有关。
Background information. Emerin is a nuclear envelope protein that contributes to nuclear architecture, chromatin structure, and gene expression through its interaction with various nuclear proteins. In particular, emerin is molecularly connected with the nuclear lamina, a protein meshwork composed of lamins and lamin-binding proteins underlying the inner nuclear membrane. Among nuclear lamina components, lamin A is a major emerin partner. Lamin A, encoded by the LMNA gene (lamin A/C gene), is produced as a precursor protein (prelamin A) that is post-transcriptionally modified at its C-terminal region where the CaaX motif triggers a sequence of modifications, including farnesylation, carboxymethylation, and proteolytic cleavage by ZMPSTE 24 (zinc metalloproteinase Ste24) metalloproteinase. Impairment of the lamin A maturation pathway causing lamin A precursor accumulation is linked to the development of rare diseases such as familial partial lipodystrophy, MADA (mandibuloacral dysplasia), the Werner syndrome, Hutchinson-Gilford progeria syndrome and RD (restrictive dermopathy).Results. In the present study, we show that emerin and different prelamin A forms influence each other's localization. We show that the accumulation of non-farnesylated as well as farnesylated carboxymethylated lamin A precursors in human fibroblasts modifies emerin localization. On the contrary, emerin absence at the inner nuclear membrane leads to unprocessed (non-farnesylated) prelamin A aberrant localization only. Moreover, we observe that the restoration of emerin expression in emerin-null cells induces the recovery of non-farnesylated prelamin A localization.Conclusion. These results indicate that emerin-prelamin A interplay influences nuclear organization. This finding may be relevant to the understanding of laminopathies.