AlphaS1-casein deficiency recorded for defective genotypes induces a chronic ER stress and deep changes in milk composition, signing a singular secretion process in goats

The extensive polymorphism recorded at the CSN1S1 locus has been shown to influence goat milk composition and its technological properties. A deficit in alphaS1-casein is responsible for the accumulation of immature caseins in distended rough endoplasmic reticulum (ER) cisternae of mammary epithelial cells (MEC). This triggers a chronic ER stress which induces, in turn, an adaptive unfolded protein response (UPR). Our data strongly suggest: i) the existence of a membraneassociated form of alphaS1-casein, which is required for efficient export of the other caseins from the ER to the Golgi apparatus; ii) that alphaS1-casein plays a key role in the early steps of casein micelle biogenesis. A differential proteomic analysis (2D-DIGE) of milks from goats of extreme genotypes (A/A vs. O/O) at the CSN1S1 locus revealed the over representation of ER-resident proteins in O/O milks, strongly suggesting a singular secretion mechanism for this genotype. In addition, goats of O/O genotype produce fat globules smaller in size and displaying significant differences in MFGM composition, including both MFGM proteins and polar lipids. A relationship between genotypes at the CSN1S1 locus and the profile (structure and composition) of milk free oligosaccharides (OS), which are also built within the ER, has been shown, thus providing additional evidence for the impact of alphaS1-casein deficiency on the functioning of MEC.