Organellar Contacts of Milk Lipid Droplets.
Organellar Contacts of Milk Lipid Droplets.
复制标题
DOI：
10.1177/2515256419897226
复制
发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
McManaman, James L
中科院分区：
文献类型：
--
作者：
Monks, Jenifer;Ladinsky, Mark S;McManaman, James L
乳腺分泌乳汁的上皮细胞在功能上专门用于合成和分泌大量中性脂质，中性脂质是大多数哺乳动物乳汁中的主要常量营养素。乳脂质的合成和分泌受垂体调节，分泌通过独特的顶浆分泌机制进行。中性脂质在粗面内质网（ER）的特化池域内合成并包装成周脂蛋白-2（PLIN 2）包被的细胞质脂滴。通过ER膜酶的持续脂质合成和脂滴融合有助于这些细胞质脂滴的大尺寸（直径5-15 μ m）。脂滴在上皮细胞内定向运输至顶端质膜。一旦接触，分子对接复合物组装以将液滴拴系到质膜并促进其膜粘附。这种对接复合物由跨膜蛋白、亲丁酸蛋白、细胞质管家蛋白、黄嘌呤脱氢酶/氧化还原酶、脂滴外壳蛋白、PLIN 2和细胞死亡诱导DFFA样效应物A组成。线粒体、高尔基体和分泌囊泡与停靠的脂滴的相互作用也已被报道，并且可以为脂滴的顶浆分泌提供膜磷脂、能量或支架细胞骨架。脂滴最终分泌到乳汁中是对催产素刺激的乳汁分泌上皮细胞周围的肌上皮细胞收缩的反应。目前尚不清楚脂滴释放的机制细节。最终分泌的乳脂球由甘油三酯核心组成，其被磷脂单层和各种外壳蛋白包被，完全包裹在膜双层中。
Milk-secreting epithelial cells of the mammary gland are functionally specialized for the synthesis and secretion of large quantities of neutral lipids, a major macronutrient in milk from most mammals. Milk lipid synthesis and secretion are hormonally regulated and secretion occurs by a unique apocrine mechanism. Neutral lipids are synthesized and packaged into perilipin-2 (PLIN2) coated cytoplasmic lipid droplets within specialized cisternal domains of rough endoplasmic reticulum (ER). Continued lipid synthesis by ER membrane enzymes and lipid droplet fusion contribute to the large size of these cytoplasmic lipid droplets (5-15 mum in diameter). Lipid droplets are directionally trafficked within the epithelial cell to the apical plasma membrane. Upon contact, a molecular docking complex assembles to tether the droplet to the plasma membrane and facilitate its membrane envelopment. This docking complex consists of the transmembrane protein, butyrophilin, the cytoplasmic housekeeping protein, xanthine dehydrogenase/oxidoreductase, the lipid droplet coat proteins, PLIN2, and cell death-inducing DFFA-like effector A. Interactions of mitochondria, Golgi, and secretory vesicles with docked lipid droplets have also been reported and may supply membrane phospholipids, energy, or scaffold cytoskeleton for apocrine secretion of the lipid droplet. Final secretion of lipid droplets into the milk occurs in response to oxytocin-stimulated contraction of myoepithelial cells that surround milk-secreting epithelial cells. The mechanistic details of lipid droplet release are unknown at this time. The final secreted milk fat globule consists of a triglyceride core coated with a phospholipid monolayer and various coat proteins, fully encased in a membrane bilayer.