Pex30-like proteins function as adaptors at distinct ER membrane contact sites.
Pex30-like proteins function as adaptors at distinct ER membrane contact sites.
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DOI：
10.1083/jcb.202103176
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发表时间：
2021-10-04
期刊：
影响因子：
--
通讯作者：
Carvalho P
中科院分区：
文献类型：
--
作者：
Ferreira JV;Carvalho P
内质网与其他细胞器(如脂滴和过氧化物体)之间的膜接触部位(MCSs)是维持脂质稳态所必需的。这项研究表明，Pex30蛋白家族的成员可以作为细胞器特异性的Pex30适配子，使其能够在多个MCS上发挥作用。内质网中合成的膜脂和蛋白质用于细胞器的从头组装，如脂滴和过氧化物体。组装后，这些细胞器的生长得到膜接触部位(MCSs)转移的内质网衍生脂的支持。细胞器生物发生和脂质转移的内质网部位是如何建立和调控的还不清楚。在这里，我们研究了内质网膜蛋白Pex30及其家族成员Pex28、Pex29、Pex31和Pex32是如何在多个MCSs靶向和发挥作用的。我们证明了不同的Pex30复合体在不同的ER结构域和MCS上发挥作用。Pex30与Pex28和Pex32结合时靶向ER-peroxisome MCSs，当与Pex29结合时组织核-空泡连接，并促进脂滴的独立于其他家族成员的生物发生。重要的是，网状同源结构域(RHD)介导了各种Pex30复合体的组装。鉴于RHD在膜成形中的作用，我们的发现提供了MCS和膜曲率调节之间的机制联系。
Membrane contact sites (MCSs) between the ER and other organelles, such as lipid droplets and peroxisomes, are essential for lipid homeostasis. This study shows that members of the Pex30 family of ER proteins function as organelle-specific adaptors for Pex30, enabling it to function at multiple MCSs. Membrane lipids and proteins synthesized in the ER are used for de novo assembly of organelles, such as lipid droplets and peroxisomes. After assembly, the growth of these organelles is supported by ER-derived lipids transferred at membrane contact sites (MCSs). How ER sites for organelle biogenesis and lipid transfer are established and regulated is unclear. Here, we investigate how the ER membrane protein Pex30 and its family members Pex28, Pex29, Pex31, and Pex32 target and function at multiple MCSs. We show that different Pex30 complexes function at distinct ER domains and MCSs. Pex30 targets ER–peroxisome MCSs when bound to Pex28 and Pex32, organizes the nuclear–vacuolar junction when bound to Pex29, and promotes the biogenesis of lipid droplets independently of other family members. Importantly, the reticulon homology domain (RHD) mediates the assembly of the various Pex30 complexes. Given the role of RHD in membrane shaping, our findings offer a mechanistic link between MCS and regulation of membrane curvature.
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影响因子：
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作者：
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DOI：
10.1083/jcb.201502070
发表时间：
2015-11-23
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
Carvalho P
DOI：
10.1083/jcb.201602064
发表时间：
2016-11-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Prinz WA