INRA, UR1196 Génomique et Physiologie de la Lactation, 78352, Jouy-en-Josas Cedex, France,
J Mammary Gland Biol Neoplasia. 2014 Mar;19(1):119-30. doi: 10.1007/s10911-013-9311-7. Epub 2013 Nov 22.
During lactation, polarized mammary epithelial secretory cells (MESCs) secrete huge quantities of the nutrient molecules that make up milk, i.e. proteins, fat globules and soluble components such as lactose and minerals. Some of these nutrients are only produced by the MESCs themselves, while others are to a great extent transferred from the blood. MESCs can thus be seen as a crossroads for both the uptake and the secretion with cross-talks between intracellular compartments that enable spatial and temporal coordination of the secretion of the milk constituents. Although the physiology of lactation is well understood, the molecular mechanisms underlying the secretion of milk components remain incompletely characterized. Major milk proteins, namely caseins, are secreted by exocytosis, while the milk fat globules are released by budding, being enwrapped by the apical plasma membrane. Prolactin, which stimulates the transcription of casein genes, also induces the production of arachidonic acid, leading to accelerated casein transport and/or secretion. Because of their ability to form complexes that bridge two membranes and promote their fusion, SNARE (Soluble N-ethylmaleimide-Sensitive Factor Attachment Protein Receptor) proteins are involved in almost all intracellular trafficking steps and exocytosis. As SNAREs can bind arachidonic acid, they could be the effectors of the secretagogue effect of prolactin in MESCs. Indeed, some SNAREs have been observed between secretory vesicles and lipid droplets suggesting that these proteins could not only orchestrate the intracellular trafficking of milk components but also act as key regulators for both the coupling and coordination of milk product secretion in response to hormones.
在哺乳期，极化的乳腺上皮分泌细胞（MESC）分泌大量构成乳汁的营养分子，即蛋白质、脂肪球和可溶性成分，如乳糖和矿物质。这些营养物质有些是由 MESC 本身产生的，而有些则在很大程度上从血液中转移而来。因此，MESC 可以被视为吸收和分泌的交汇点，细胞内隔室之间存在着交流，从而使乳汁成分的分泌在空间和时间上协调一致。尽管泌乳生理学已被很好地理解，但乳汁成分分泌的分子机制仍未完全阐明。主要的乳蛋白，即酪蛋白，通过胞吐作用分泌，而乳脂肪球则通过出芽释放，被顶端质膜包裹。催乳素刺激酪蛋白基因的转录，也诱导花生四烯酸的产生，导致酪蛋白的运输和/或分泌加速。由于它们能够形成桥接两个膜并促进融合的复合物，SNARE（可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体）蛋白参与几乎所有的细胞内运输步骤和胞吐作用。由于 SNARE 可以结合花生四烯酸，它们可能是催乳素在 MESC 中促分泌作用的效应物。事实上，已经观察到一些 SNARE 存在于分泌小泡和脂滴之间，这表明这些蛋白不仅可以协调乳汁成分的细胞内运输，还可以作为关键调节剂，协调激素刺激下乳汁产物分泌的偶联和协调。
