Multiple C2 domain-containing transmembrane proteins promote lipid droplet biogenesis and growth at specialized endoplasmic reticulum subdomains.
Multiple C2 domain-containing transmembrane proteins promote lipid droplet biogenesis and growth at specialized endoplasmic reticulum subdomains.
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多个含C2结构域的跨膜蛋白在专门的内质网亚结构域促进脂滴生物发生和生长。
DOI：
10.1091/mbc.e20-09-0590
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发表时间：
2021-06-01
影响因子：
3.3
通讯作者：
Cohen S
中科院分区：
文献类型：
--
作者：
Joshi AS;Ragusa JV;Prinz WA;Cohen S
脂滴（LD）是包裹在单层磷脂中的中性含脂细胞器。LD的形成始于中性脂质在内质网（ER）膜双层内的积累。目前尚不清楚如何确定ER膜中新生LD的形成位点。在这里，我们表明，多个C2结构域的跨膜蛋白，MCTP 1和MCTP 2，是在网站的LD形成专门的ER亚结构域。我们发现，这些蛋白质的跨膜结构域（TMD）是类似的reticulon同源结构域。像网织蛋白一样，这些蛋白质使内质网膜形成管状，并有利于内质网的高度弯曲区域。我们的数据表明，MCTP TMD促进LD生物合成，增加LD数量。MCTP与参与LD生物发生的蛋白质seipin共定位，但在ER中形成更稳定的微结构域。MCTP C2结构域结合带电脂质并调节LD大小，可能通过介导ER-LD接触位点。总之，我们的数据表明MCTP在ER小管内形成微区，调节LD生物发生，大小和ER-LD接触。有趣的是，MCTP点共定位与其他细胞器，以及，这表明这些蛋白质可能在连接管状ER细胞器接触网站的一般作用。
Lipid droplets (LDs) are neutral lipid-containing organelles enclosed in a single monolayer of phospholipids. LD formation begins with the accumulation of neutral lipids within the bilayer of the endoplasmic reticulum (ER) membrane. It is not known how the sites of formation of nascent LDs in the ER membrane are determined. Here we show that multiple C2 domain–containing transmembrane proteins, MCTP1 and MCTP2, are at sites of LD formation in specialized ER subdomains. We show that the transmembrane domain (TMD) of these proteins is similar to a reticulon homology domain. Like reticulons, these proteins tubulate the ER membrane and favor highly curved regions of the ER. Our data indicate that the MCTP TMDs promote LD biogenesis, increasing LD number. MCTPs colocalize with seipin, a protein involved in LD biogenesis, but form more stable microdomains in the ER. The MCTP C2 domains bind charged lipids and regulate LD size, likely by mediating ER–LD contact sites. Together, our data indicate that MCTPs form microdomains within ER tubules that regulate LD biogenesis, size, and ER–LD contacts. Interestingly, MCTP punctae colocalized with other organelles as well, suggesting that these proteins may play a general role in linking tubular ER to organelle contact sites.