Organellar Contacts of Milk Lipid Droplets

Abstract

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 lm 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 oxytocinstimulated 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.

Perilipin-2 promotes lipid droplet-plasma membrane interactions that facilitate apocrine lipid secretion in secretory epithelial cells of the mouse mammary gland

“…A distinctive feature of apocrine LD secretion by sMEC is the formation of stable, electron-dense 10-20 nm contacts between the LD and the apical plasma membrane (APM) (Wooding 1971) that induce alterations in the plasma membrane structure and spatial remodeling of integral membrane proteins and the glycocalyx (Peixoto de Menezes and Pinto da Silva 1978; Mather and Keenan 1998;Monks, et al, 2016), which are proposed to facilitate the apocrine secretion process (Vorbach, et al, 2002;Ogg, et al, 2004;Monks, et al, 2016). However, significant gaps remain in our understanding of the molecular and structural features that define LD-APM contacts, the mechanisms governing their formation and stabilization, and the functional relationships between membrane contact, envelopment, and secretion of LD (Monks, et al, 2020).…”

Hybrid Broussonetia papyrifera Fermented Feed Can Play a Role Through Flavonoid Extracts to Increase Milk Production and Milk Fatty Acid Synthesis in Dairy Goats

“…Hybrid B. papyrifera flavone may have a similar effect, which can promote the mutual conversion of nutrients and increase the synthesis of milk fat. Cytoplasmic lipid droplet's is the direct precursors of milk lipids and are the storage place for newly formed lipids and other neutral lipids ( 50 ). The epithelial cells that secrete milk in the mammary gland have the function of synthesizing and secreting large amounts of neutral lipids, which are the main macronutrients in most mammalian milk.…”

Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) regulates acetate- and β-hydroxybutyrate-induced milk fat synthesis by increasing FASN expression in mammary epithelial cells of dairy cows

“…The TAG is synthesized in or on the surfaces of rough endoplasmic reticulum membranes and is released into the cytoplasm as microlipid droplets with a surface coat of protein and polar lipid (Mather and Keenan, 1998). Then, the microlipid droplets in mammary epithelial cells fuse with each other to form larger cytoplasmic lipid droplets (Monks et al, 2020). The lipid droplet size affects the physiochemical characteristics of dairy products as well as the aggregation and coalescence properties of milk (O'Mahony et al, 2005;Couvreur and Hurtaud, 2017).…”