Reticulon short hairpin transmembrane domains are used to shape ER tubules.

Reticulon short hairpin transmembrane domains are used to shape ER tubules.
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DOI:
10.1111/j.1600-0854.2010.01134.x
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发表时间:
2011-01
期刊:
Traffic (Copenhagen, Denmark)
影响因子:
--
通讯作者:
Voeltz G
Voeltz G
中科院分区:
其他
文献类型:
--
作者:
Zurek N;Sparks L;Voeltz G

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网织蛋白是完整的膜蛋白,可划分并塑造管状内质网 (ER)。我们建议网状体使用膜插入机制在内质网中产生高膜曲率区域。 Reticulon 含有两个短发夹跨膜结构域(TMD),可以通过增加细胞质小叶的面积来产生膜曲率。在这里,我们测试了这些发夹 TMD 的短长度是否是哺乳动物细胞中网织膜成形功能所必需的。我们延长了 Reticulon 4 的 TMD,使其类似于跨越两个小叶的典型双通 TMD。我们发现TMD突变体像wt一样寡聚,但它们不固定,不分成小管,不收缩小管,并且不再抑制外周ER池。因此,网状蛋白的分配和膜成形功能需要短的发夹TMD长度。另一种带有短发夹TMD的膜蛋白是caveolin。我们证明了 ER 保留的小窝蛋白构建体也在 ER 内以依赖于它包含短发夹 TMD 的方式进行分区。这些数据表明,短发夹TMD可能是膜成形蛋白用来划分和塑造高膜曲率区域的一般特征。
Reticulons are integral membrane proteins that partition into and shape the tubular endoplasmic reticulum (ER). We propose that reticulons use a membrane-insertion mechanism to generate regions of high membrane curvature in the ER. Reticulon contains two short hairpin transmembrane domains (TMD), which could generate membrane curvature by increasing the area of the cytoplasmic leaflet. Here, we test whether the short length of these hairpin TMDs is required for reticulon membrane-shaping functions in mammalian cells. We lengthened the TMDs of Reticulon 4 to resemble a typical bi-pass TMD that spans both leaflets. We find that TMD mutants oligomerize like wt, however they are not immobilized, do not partition into tubules, do not constrict tubules, and no longer suppress peripheral ER cisternae. Therefore, short hairpin TMD length is required for reticulon protein partitioning and membrane shaping functions. Another membrane protein with a short hairpin TMD is caveolin. We demonstrate that an ER-retained caveolin construct also partitions within the ER in a manner that is dependent on it containing a short hairpin TMD. These data suggest that a short hairpin TMD may be a general feature used by membrane-shaping proteins to partition into and shape regions of high membrane curvature.
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